Oxazolidinone antibacterial agents having a thiocarbonyl funtionality

ABSTRACT

The present invention provides compounds of Formula 1                    
     or pharmaceutical acceptable salts thereof wherein A, G and R 1  are as defined in the claims which are antibacterial agents.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of U.S. patent applicationSer. No: 09/200,904, filed Nov. 27, 1998 U.S. Pat. No. 6,255,304; whichis a continuation-in-part of co-pending application U.S. Ser. No.09/080,751, filed May 18, 1998U.S. Pat. No. 6,218,413, which claims thebenefit of provisional application U.S. Serial No. 60/048,342, filed May30, 1997, under 35 USC 119(e)(i).

BACKGROUND OF THE INVENTION

The present invention relates to new and useful oxazolidinone compoundsand their preparations, and more particularly to oxazolidinone compoundsin which the carbonyl functionality of —NH—C(O)—R is converted to athiocarbonyl functionality, such as a thiourea —NH—C(S)—NH₂, an alkylthiourea —NH—C(S)—NH—(C₁₋₄ alkyl), thioamide —NH—C(S)—(C₁₋₄ alkyl) or—NH—C(S)—H.

Replacement of the oxygen atom with a sulfur atom has unexpectedlyimproved the antimicrobial properties of the compounds. The compoundsare useful antimicrobial agents, effective against a number of human andveterinary pathogens, including Gram-positive aerobic bacteria such asmultiply-resistant staphylococci and streptococci, Gram-negativeorganisms such as H. influenzae and M. catarrahlis as well as anaerobicorganisms such as bacteroides and clostridia species, and acid-fastorganisms such as Mycobacterium tuberculosis and Mycobacterium avium.The compounds are particularly useful because they are effective againstthe latter organisms which are known to be responsible for infection inpersons with AIDS.

SUMMARY OF THE INVENTION

In one aspect the subject invention is a compound of the Formula I

or pharmaceutical acceptable salts thereof wherein:

R₁ is

a) H,

b) NH₂,

c) NH—C₁₋₄ alkyl,

d) C₁₋₄ alkyl,

e) —OC₁₋₄ alkyl,

f) —S C₁₋₄ alkyl,

g) C₁₋₄ alkyl substituted with 1-3 F, 1-2 Cl, CN or —COOC₁₋₄ alkyl,

h) C₃₋₆ cycloalkyl,

i) N(C₁₋₄ alkyl)₂ or

j) N(CH₂)₂₋₅;

d) a 5-membered heteroaromatic moiety having one to three atoms selectedfrom the group consisting of S, N, and O,

wherein the 5-membered heteroaromatic moiety is bonded via a carbonatom,

wherein the 5-membered heteroaromatic moiety can additionally have afused-on benzene or naphthyl ring,

wherein the heteroaromatic moiety is optionally substituted with one tothree R₄₈,

e) a 6-membered heteroaromatic moiety having at least one nitrogen atom,

wherein the heteroaromatic moiety is bonded via a carbon atom,

wherein the 6-membered heteroaromatic moiety can additionally havefused-on benzene or naphthyl ring,

wherein the heteroaromatic moiety is optionally substituted with one tothree R₅₅,

f) a β-carbolin-3-yl, or indolizinyl bonded via the 6-membered ring,optionally substituted with one to three R₅₅,

wherein R₂ is

a) H,

b) F,

c) Cl,

d) Br,

e) C₁₋₃ alkyl,

f) NO₂, or

g) R₂ and R₃ taken together are —O—(CH₂)_(h)—O—;

R₃ is

a) —S(═O)_(i) R₄,

b) —S(═O)₂—N═S(O)_(j)R₅R₆,

c) —SC(═O)R₇,

d) —C(═O)R₈,

e) —C(═O)R₉,

f) —C(═O)NR₁₀R₁₁,

g) —C(═NR₁₂)R₈,

h) —C(R₈)(R₁₁)—OR₁₃,

i) —C(R₉)(R₁₁)—OR₁₃,

j) —C(R₈)(R₁l)—OC(═O)R₁₃,

k) —C(R₉)(R₁₁)—OC(═O)R₁₃,

l) —NR₁₀R₁₁,

m) —N(R₁₀)—C(═O)R₇,

n) —N(R₁₀)—S(═O)_(i)R₇,

o) —C(OR₁₄)(OR₁₅)R₈,

p) —C(R₈)(R₁₆)—NR₁₀R₁₁, or

q) C₁₋₈ alkyl substituted with one or more ═O other than at alphaposition, —S(═O)_(i)R₁₇, —NR₁₀R₁₁, C₂₋₅ alkenyl, or C₂₋₅ alkynyl;

R₄ is

a) C₁₋₄ alkyl optionally substituted with one or more halos, OH, CN,NR₁₀R₁₁, or —CO₂R₁₃,

b) C₂₋₄ alkenyl,

c) —NR₁₆R₁₈,

d) —N₃,

e) —NHC(═O)R₇,

f) —NR₂₀(═O)R₇,

g) —N(R₁₉)₂,

h) —NR₁₆R₁₉, or

i) —NR₁₉R₂₀,

R₅ and R₆ at each occurrence are the same or different and are

a) C₁₋₂ alkyl, or

b) R₅ and R₆ taken together are —(CH₂)_(k)—;

R₇ is C₁₋₄ alkyl optionally substituted with one or more halos;

R₈ is

a) H, or

b) C₁₋₈ alkyl optionally substituted with one or more halos, or C₃₋₈cycloalkyl;

R₉ is C₁₋₄ alkyl substituted with one or more

a) —S(═O)R₁₇,

b) —OR₁₃,

c) —OC(═O)R₁₃,

d) —NR₁₀R₁₁, or

e) C₁₋₅ alkenyl optionally substituted with CHO;

R₁₀ and R₁₁ at each occurrence are the same or different and are

a) H,

b) C₁₋₄ alkyl, or

c) C₃₋₈ cycloalkyl;

R₁₂ is

a) —NR₁₀R₁₁,

b) —OR₁₀; or

c) —NHC(═O)R₁₀;

R₁₃ is

a) H, or

b) C₁₋₄ alkyl;

R₁₄ and R₁₅ at each occurrence are the same or different and are

a) C₁₋₄ alky, or

b) R₁₄ and R₁₅ taken together are —(CH)_(l)—;

R₁₆ is

a) H,

b) C₁₋₄ alkyl, or

c) C₃₋₈ cycloalkyl;

R₁₇ is

a) C₁₋₄ alkyl, or

b) C₃₋₈ cycloalkyl;

R₁₈ is

a) H,

b) C₁₋₄ alkyl,

c) C₂₋₄ alkenyl,

d) C₃₋₄ cycloalkyl,

e) —OR₁₃ or

f) —NR₂₁R₂₂;

R₁₉, is

a) Cl,

b) Br, or

c) I;

R₂₀ is a physiologically acceptable cation;

R₂₁ and R₂₂ at each occurrence are the same or different and are

a) H,

b) C₁₋₄ alkyl, or

c) —NR₂₁R₂₂ taken together are —(CH₂)_(m)—;

wherein R₂₃ and R₂₄ at each occurrence are the same or different and are

a) H,

b) F,

c) Cl,

d) C₁₋₂ alkyl,

e) CN

f) OH,

g) C₁₋₂ alkoxy,

h) nitro, or

i) amino;

m) a diazinyl group optionally substituted with X and Y,

n) a triazinyl group optionally substituted with X and Y,

o) a quinolinyl group optionally substituted with X and Y,

p) a quinoxalinyl group optionally substituted with X and Y,

q) a naphthyridinyl group optionally substituted with X and Y,

Q and R₂₄ taken together are

 wherein Z¹ is

a) —CH₂—,

b) —CH(R¹⁰⁴)—CH₂—,

c) —C(O)—, or

d) —CH₂CH₂CH₂—;

wherein Z² is

a) —O₂S—,

b) —O—,

c) —N(R¹⁰⁷)—,

d) —OS—, or

e) —S—;

wherein Z³ is

a) —O₂S—,

b) —O—,

c) —OS—, or

d) —S—;

wherein A¹ is

a) H—, or

b) CH₃;

wherein A² is

a) H—,

b) HO—,

c) CH₃—,

d) CH₃O—,

e) R¹⁰²O—CH₂—C(O)—NH—

f) R¹⁰³O—C(O)—NH—,

g) (C₁-C₂)alkyl-O—C(O)—,

h) HO—CH₂—,

i) CH₃O—NH—,

j) (C₁-C₃)alkyl-O₂C—

k) CH₃—C(O)—,

l) CH₃—C(O)—CH₂—,

A¹ and A² taken together are:

wherein R¹⁰² is

a) H—,

b) CH₃—,

c) phenyl-CH₂—, or

d) CH₃C(O)—;

wherein R¹⁰³ is

a) (C₁-C₃)alkyl-, or

b) phenyl-;

wherein R¹⁰⁴ is

a) H—, or

b) HO—;

wherein R¹⁰⁵ is

a) H—,

b) (C₁-C₃)alkyl-,

c) CH₂═CH—CH₂-, or

d) CH₃—O—(CH₂)₂—;

wherein R¹⁰⁶ is

a) CH₃—C(O)—,

b) H—C(O)—,

c) Cl₂CH—C(O)—,

d) HOCH₂—C(O)—,

e) CH₃SO₂—,

g) F₂CHC(O)—,

i) H₃C—C(O)—O—CH₂—C(O)—,

j) H—C(O)—O—CH₂—C(O)—,

l) HC≡C—CH₂O—CH₂—C(O)—, or

m) phenyl-CH₂—O—CH₂—C(O)—;

wherein R¹⁰⁷ is

a) R¹⁰²O—C(R¹¹⁰)(R¹¹¹)—C(O)—,

b) R¹⁰³O—C(O)—,

c) R¹⁰⁸—C(O)—,

f) H₃C—C(O)—(CH₂)₂—C(O)—,

g) R¹⁰⁹—SO₂—,

i) HO—CH₂—C(O)—,

j) R¹¹⁶—(CH₂)₂—,

k) R¹¹³—C(O)—O—CH₂—C(O)—,

l) (CH₃)₂N—CH₂—C(O)—NH—,

m) NC—CH₂—,

n) F₂—CH—CH₂—, or

o) R¹⁵⁰R¹⁵¹NSO₂

wherein R¹⁰⁸ is

a) H—,

b) (C₁-C₄)alkyl,

c) aryl —(CH₂)_(p),

d) ClH₂C—,

e) Cl₂HC—,

f) FH₂C—,

g) F₂HC—,

h) (C₃-C₆)cycloalkyl, or

i) CNCH₂—.

wherein R¹⁰⁹ is

a) alkylC₁-C₄,

b) —CH₂Cl

c) —CH₂CH═CH₂,

d) aryl, or

e) —CH₂CN;

wherein R¹¹⁰ and R¹¹¹ are independently

a) H—,

b) CH₃—; or

wherein R¹¹² is

a) H—,

b) CH₃O—CH₂O—CH₂—, or

c) HOCH₂—;

wherein R¹¹³ is

a) CH₃—,

b) HOCH₂—,

c) (CH₃)₂N-phenyl, or

d) (CH₃)₂N—CH₂—;

wherein R¹¹⁴ is

a) HO—,

b) CH₃O—,

c) H₂N—,

d) CH₃O—C(O)—O—,

e) CH₃—C(O)—O—CH₂—C(O)—O—,

f) phenyl-CH₂—O—CH₂—C(O)—O—,

g) HO—(CH₂)₂—O—,

h) CH₃O—CH₂—O—(CH₂)₂—O—, or

i) CH₃O—CH₂—O—;

wherein R¹¹³ is

a) CH₃—,

b) HOCH₂—,

c) (CH₃)₂N-phenyl, or

d) (CH₃)₂N—CH₂—;

wherein R¹¹⁵ is

a) H—, or

b) Cl—;

wherein R¹¹⁶ is

a) HO—

b) CH₃O—, or

c) F;

wherein R¹⁵⁰ and R¹⁵¹ are each H or alkyl C₁-C₄ or R¹⁵⁰ and R¹⁵¹ takentogether with the nitrogen atom to which each is attached form amonocyclic heterocyclic ring having from 3 to 6 carbon atoms;

B is an unsaturated 4-atom liner having one nitrogen and three carbons;

M is

a) H,

b) C₁₋₈ alkyl,

c) C₃₋₈ cycloalkyl,

d) —(CH₂)_(m)OR₁₃, or

e) —(CH₂)_(h)—NR₂₁R₂₂;

Z is

a) O,

b) S, or

c) NM;

W is

a) CH,

b) N, or

c) S or O when Z is NM;

Y is

a) H,

b) F,

c) Cl,

d) Br,

e) C₁₋₃ alkyl, or

f) NO₂;

X is

a) H,

b) —CN,

c) OR₂₇,

d) halo,

e) NO₂,

f) tetrazoyl,

g) —SH,

h) —S(═O)_(i)R₄,

i) —S(═O)₂—N═S(O)_(j)R₅R₆,

j) —SC(═O)R₇,

k) —C(═O)R_(25,)

l) —C(═O)NR₂₇R₂₈,

m) —C(═NR₂₉)R₂₅,

n) —C(R₂₅)(R₂₈)—OR₁₃,

o) —C(R₂₅)(R₂₈)—OC(═O)R₁₃,

p) —C(R₂₈)(OR₁₃)—(CH₂)_(h)—NR₂₇R₂₈,

q) —NR₂₇R₂₈,

r) —N(R₂₇)C(═O)R₇,

s) —N(R₂₇)—S(═O)_(i)R₇,

t) —C(OR₁₄)(OR₁₅)R₂₈,

u) —C(R₂₅)(R₁₆)—NR₂₇R₂₆, or

v) C₁₋₈ alkyl substituted with one or more halos, OH, ═O other than atalpha position, —S(═O)_(i)R₁₇, —NR₂₇R₂₈, C₂₋₅ alkenyl, C₂₋₅ alkynyl, orC₃₋₈ cycloalkyl;

R₄, R₅, R₆, R₇, R₁₃, R₁₄, R₁₅, R₁₆, and R₁₇ are the same as definedabove;

R₂₅ is

a) H,

b) C₁₋₈ alkyl optionally substituted with one or more halos, C₃₋₈cycloalkyl, C₁₋₄ alkyl substituted with one or more of —S(═O)_(i)R₁₇,—OR₁₃, or OC(═O)R₁₃, N₂₇R₂₈, or

c) C₂₋₅ alkenyl optionally substituted with CHO, or CO₂R₁₃;

R₂₆ is

a) R₂₈, or

b) NR₂₇N₂₈;

R₂₇ and R₂₈ at each occurrence are the same or different and are

a) H,

b) C₁₋₈ alkyl,

c) C₃₋₈ cycloalkyl,

d) —(CH₂)_(m)OR₁₃,

e) —(CH₂)_(h)—NR₂₁R₂₂, or

f) R₂₇ and R₂₈ taken together are —(CH₂)₂O(CH₂)₂—, —(CH₂)_(h)CH(COR₇)—,or —(CH₂)₂N(CH₂)₂(R₇);

R₂₉ is

a) —NR₂₇R₂₈,

b) —OR₂₇, or

c) —NHC(═O)R₂₈;

wherein R₃₀ is

a) H,

b) C₁₋₈ alkyl optionally substituted with one or more halos, or

c) C₁₋₈ alkyl optionally substituted with one or more OH, or C₁₋₆alkoxy;

wherein E is

a) NR₃₉,

b) —S(═O)_(i), or

c) O;

R₃₈ is

a) H,

b) C₁₋₆ alkyl,

c) —(CH₂)_(q)-aryl, or

d) halo;

R₃₉ is

a) H,

b) C₁₋₆ alkyl optionally substituted with one or more OH, halo, or —CN,

c) —(CH₂)_(q)-aryl,

d) —CO₂R₄₀,

e) —COR₄₁,

f) C(═O)—(CH₂)_(q)—C(═O)R₄₀,

g) —S(═O)₂—C₁₋₆ alkyl,

h) —S(═O)₂—(CH₂)_(q)-aryl, or

i) —(C═O)_(j)-Het;

R₄₀ is

a) H,

b) C₁₋₆ alkyl optionally substituted with one or more OH, halo, or —CN,

c) —(CH₂)_(q)-aryl, or

d) —(CH₂)_(q)—OR₄₂;

R₄₁ is

a) C₁₋₆ alkyl optionally substituted with one or more OH, halo, or —CN,

b) —(CH₂)_(q)-aryl, or

c) —(CH₂)_(q)—OR₄₂;

R₄₂ is

a) H,

b) C₁₋₆ alkyl,

c) —(CH₂)_(q)-aryl, or

d) —C(═O)—C₁₋₆ alkyl;

aryl is

a) phenyl,

b) pyridyl, or

c) napthyl; a to c optionally substituted with one or more halo, —CN,OH, SH, C₁₋₆ alkyl, C₁₋₆ alkoxy, or C₁₋₆ alkylthio;

wherein R₄₃ is

a) H,

b) C₁₋₂ alkyl,

c) F, or

d) OH;

R₄₄ is

a) H,

b) CF₃,

c) C₁₋₃ alkyl optionally substituted with one or more halo,

d) phenyl optionally substituted with one or more halo,

e) R₄₄ and R₄₅ taken together are a 5-, 6-, or 7-membered ring of theformula,

f) R₄₄ and R₄₅ taken together are —(CH₂)_(k)—, when R₄₆ is anelectron-withdrawing group;

R₄₅ and R₄₆ at each occurrence are the same or different and are

a) an electron-withdrawing group,

b) H,

c) CF₃,

d) C₁₋₃ alkyl optionally substituted with one halo,

e) phenyl, provided at least one of R₄₅ or R₄₆ is anelectron-withdrawing group, or

f) R₄₅ and R₄₆ taken together are a 5-, 6-, 7-membered ring of theformula

U is

a) CH₂,

b) O,

c) S, or

d) NR₄₇;

R₄₇ is

a) H, or

b) C₁₋₅ alkyl;

wherein R₄₈ is

a) carboxyl,

b) halo,

c) —CN,

d) mercapto,

e) formyl,

f) CF₃,

g) —NO₂,

h) C₁₋₆ alkoxy,

i) C₁₋₆ alkoxycarbonyl,

j) C₁₋₆ alkythio,

k) C₁₋₆ acyl,

l) —NR₄₉ R₅₀,

m) C₁₋₆ alkyl optionally substituted with OH, C₁₋₅ alkoxy, C₁₋₅ acyl, or—NR₄₉R₅₀,

n) C₂₋₈ alkenylphenyl optionally substituted with one or two R₅₁,

o) phenyl optionally substituted with one or two R₅₁,

p) a 5-, or 6-membered (un)saturated heterocyclic moiety having one tothree atoms selected from the group consisting of S, N, and O,optionally substituted with one or two R₅₁, or

R₄₉ and R₅₀ at each occurrence are the same or different and are

a) H,

b) C₁₋₄ alkyl,

c) C₅₋₆ cycloalkyl, or

d) R₄₉ and R₅₀ taken together with the nitrogen atom is a 5-, 6-memberedsaturated heterocyclic moiety which optionally has a further hetero atomselected from the group consisting of S, N, and O, and can in turn beoptionally substituted with, including on the further nitrogen atom,C₁₋₃ alkyl, or C₁₋₃ acyl;

R₅₁ is

a) carboxyl,

b) halo,

c) —CN,

d) mercapto,

e) formyl,

f) CF₃,

g) —NO₂,

h) C₁₋₆ alkoxy,

i) C₁₋₆ alkoxycarbonyl,

j) C₁₋₆ alkythio,

k) C₁₋₆ acyl,

l) C₁₋₆ alkyl optionally substituted with OH, C₁₋₅ alkoxy, C₁₋₅ acyl, or—NR₄₉R₅₀,

m) phenyl,

n) —C(═O)NR₅₂ R₅₃,

o) —NR₄₉R₅₀,

p) —N(R₅₂)(—SO₂R₅₄),

q) —SO₂—NR₅₂R₅₃, or

r) —S(═O)_(i)R₅₄;

R₅₂ and R₅₃ at each occurrence are the same or different and are

a) H,

b) C₁₋₆ alkyl, or

c) phenyl;

R₅₄ is

a) C₁₋₄ alkyl, or

b) phenyl optionally substituted with C₁₋₄ alkyl;

wherein R₅₅ is

a) carboxyl,

b) halo,

c) —CN,

d) mercapto,

e) formyl,

f) CF₃,

g) —NO₂,

h) C₁₋₆ alkoxy,

i) C₁₋₆ alkoxycarbonyl,

j) C₁₋₆ alkythio

k) C₁₋₆ acyl,

l) —NR₅₆R₅₇,

m) C₁₋₆ alkyl optionally substituted with OH, C₁₋₅ alkoxy, C₁₋₅ acyl, or—NR₅₆R₅₇,

n) C₂₋₈ alkenylphenyl optionally substituted with one or two R₅₈,

o) phenyl optionally substituted with one or two R₅₈,

p) a 5- or 6-membered (un)saturated heterocyclic moiety having one tothree atoms selected from the group consisting of S, N, and O,optionally substituted with one or two R₅₈, or

R₅₆ and R₅₇ at each occurrence are the same or different and are

a) H,

b) formyl,

c) C₁₋₄ alkyl,

d) C₁₋₄ acyl,

e) phenyl,

f) C₃₋₆ cycloalkyl, or

g) R₅₆ and R₅₇ taken together with the nitrogen atom is a 5-, 6-memberedsaturated heterocyclic moiety which optionally has a further hetero atomselected from the group consisting of S, N, and O, and can in turn beoptionally substituted with, including on the further nitrogen atom,phenyl, pyrimidyl, C₁₋₃ alkyl, or C₁₋₃ acyl;

R₅₈ is

a) carboxyl,

b) halo,

c) —CN,

d) mercapto,

e) formyl,

f) CF₃,

g) —NO₂,

h) C₁₋₆ alkoxy,

i) C₁₋₆ alkoxycarbonyl,

j) C₁₋₆ alkythio,

k) C₁₋₆ acyl,

l) phenyl,

m) C₁₋₆ alkyl optionally substituted with OH, azido, C₁₋₅ alkoxy, C₁₋₅acyl, —NR₆₅R₆₆, —SR₆₇, —O—SO₂R₆₈, or

n) —C(═O)NR₅₉ R₆₀,

o) —NR₅₆R₅₇,

p) —N(R₅₉)(—SO₂R₅₄),

q) —SO₂—NR₅₉R₆₀,

r) —S(═O)_(i)R₅₄,

s) —CH═N—R₆₁, or

t) —CH(OH)—SO₃R_(64;)

R₅₄ is the same as defined above;

R₅₉ and R₆₀ at each occurrence are the same or different and are

a) H,

b) C₁₋₆ alkyl,

c) phenyl, or

d) tolyl;

R₆₁ is

a) OH,

b) benzyloxy,

c) —NH—C(═O)—NH₂,

d) —NH—C(═S)—NH₂, or

e) —NH—C(═NH)—NR₆₂R₆₃;

R₆₂ and R₆₃ at each occurrence are the same or different and are

a) H, or

b) C₁₋₄ alkyl optionally substituted with phenyl or pyridyl;

R₆₄ is

a) H, or

b) a sodium ion;

R₆₅ and R₆₆ at each occurrence are the same or different and are

a) H,

b) formyl,

c) C₁₋₄ alkyl,

d) C₁₋₄ acyl,

e) phenyl,

f) C₃₋₆ cycloalkyl,

g) R₆₅ and R₆₆ taken together are a 5-, 6-membered saturatedheterocyclic moiety having one to three atoms selected from the groupconsisting of S, N, and O, optionally substituted with, including on thenitrogen atom, phenyl, pyrimidyl, C₁₋₃ alkyl, or C₁₋₃ acyl,

h) —P(O)(OR₇₀O)(OR₇₁), or

i) —SO₂—R₇₂;

R₆₈ is C₁₋₃ alkyl;

R₆₉ is

a) C₁₋₆ alkoxycarbonyl, or

b) carboxyl;

R₇₀ and R₇₁ at each occurrence are the same or different and are

a) H, or

b) C₁₋₃ alkyl;

R₇₂ is

a) methyl,

b) phenyl, or

c) tolyl;

wherein K is

a) O, or

b) S;

R₇₃, R₇₄, R₇₅, R₇₆, and R₇₇ at each occurrence are the same or differentand are

a) H,

b) carboxyl,

c) halo,

d) —CN,

e) mercapto,

f) formyl,

g) CF₃,

h) —NO₂,

i) C₁₋₆ alkoxy,

j) C₁₋₆ alkoxycarbonyl,

k) C₁₋₆ alkythio,

l) C₁₋₆ acyl,

m) —NR₇₈ R₇₉,

n) C₁₋₆ alkyl optionally substituted with OH, C₁₋₅ alkoxy, C₁₋₅ acyl,—NR₇₈R₇₉, —N(phenyl)(CH₂—CH₂—OH), —O—CH(CH₃)(OCH₂CH₃), or—O-phenyl-[para-NHC(═O)CH₃],

o) C₂₋₈ alkenylphenyl optionally substituted with R₅₁,

p) phenyl optionally substituted with R₅₁, or

q) a 5-, or 6-membered (un)saturated heterocyclic moiety having one tothree atoms selected from the group consisting of S, N, and O,optionally substituted with R₅₁;

R₅₁ is the same as defined above;

R₇₈ and R₇₉ at each occurrence are the same or different and are

a) H,

b) C₁₋₄ allyl,

c) phenyl, or

d) R₇₈ and R₇₉ taken together with the nitrogen atom is a 5-, 6-memberedsaturated heterocyclic moiety which optionally has a further hetero atomselected from the group consisting of S, N, and O, and can in turn beoptionally substituted with, including on the further nitrogen atom,C₁₋₃ alkyl, or C₁₋₃ acyl;

wherein T is

a) O,

b) S, or

c) SO₂;

R₇₅, R₇₆, and R₇₇ are the same as defined above;

R₈₀ is

a) H,

b) formyl,

c) carboxyl,

d) C₁₋₆ alkoxycarbonyl,

e) C₁₋₈ alkyl,

i) C₂₋₈ alkenyl, wherein the substituents (e) and (f) can be optionallysubstituted with OH, halo, C₁₋₆ alkoxy, C₁₋₆ acyl, C₁₋₆ alkylthio orC₁₋₆ alkoxycarbonyl, or phenyl optionally substituted with halo,

g) an aromatic moiety having 6 to 10 carbon atoms optionally substitutedwith carboxyl, halo, —CN, formyl, CF₃, —NO₂, C₁₋₆ alkyl, C₁₋₆ alkoxy,C₁₋₆ acyl, C₁₋₆ alkylthio, or C₁₋₆ alkoxycarbonyl;

h) —NR₈₁R₈₂,

i) —OR₉₀,

j) —S(═O)_(i)—R₉₁,

k) —SO₂—N(R₉₂)(R₉₃), or

l) a radical of the following formulas:

R₈₁ and R₈₂ at each occurrence are the same or different and are

a) H,

b) C₃₋₆ cycloalkyl,

c) phenyl,

d) C₁₋₆ acyl,

e) C₁₋₈ alkyl optionally substituted with OH, C₁₋₆ alkoxy which can besubstituted with OH, a 5-, or 6-membered aromatic heterocyclic moietyhaving one to three atoms selected from the group consisting of S, N,and O, phenyl optionally substituted with OH, CF₃, halo, —NO₂, C₁₋₄alkoxy, —NR₈₃R₈₄, or

b) CH₂, or

c) NR₈₇;

R₈₃ and R₈₄ at each occurrence are the same or different and are

a) H, or

b) C₁₋₄ alkyl;

R₈₅ is

a) OH,

b) C₁₋₄ alkoxy, or

c) —NR₈₈ R_(89;)

R₈₆ is

a) H, or

b) C₁₋₇ alkyl optionally substituted with indolyl, OH, mercaptyl,imidazoly, methylthio, amino, phenyl optionally substituted with OH,—C(═O)—NH₂, —CO₂H, or —C(═NH)—NH₂;

R₈₇ is

a) H,

b) phenyl, or

c) C₁₋₆ alkyl optionally substituted by OH;

R₈₈ and R₈₉ at each occurrence are the same or different and are

a) H,

b) C₁₋₅ alkyl

c) C₃₋₆ cycloalky, or

d) phenyl;

R₉₀ is

a) C₁₋₈ alkyl optionally substituted with C₁₋₆ alkoxy or C₁₋₆ hydroxy,C₃₋₆ cycloalkyl, a 6-membered aromatic optionally benzo-fusedheterocyclic moiety having one to three nitrogen atoms, which can inturn be substituted with one or two —NO₂, CF₃, halo, —CN, OH, C₁₋₅alkyl, C₁₋₅ alkoxy, or C₁₋₅ acyl;

c) phenyl, or

d) pyridyl;

R₉₁ is

a) C₁₋₁₆ alkyl,

b) C₂₋₁₆ alkenyl, wherein the substituents (a) and (b) can be optionallysubstituted with C₁₋₆ alkoxycarbonyl, or a 5-, 6-, 7-membered aromaticheterocyclic moiety having one to three atoms selected from the groupconsisting of S, N, and O,

c) an aromatic moiety having 6 to 10 carbon atoms, or

d) a 5-, 6-, 7-membered aromatic heterocyclic moiety having one to threeatoms selected from the group consisting of S, N, and O, wherein thesubstituents (c) and (d) can be optionally substituted with carboxyl,halo, —CN, formyl, CF₃, —NO₂, C₁₋₆ alkyl, C₁₋₆ alkoxy, C₁₋₆ acyl,C₁₋₆alkylthio, or C₁₋₆ alkoxycarbonyl;

R₉₂ and R₉₃ at each occurrence are the same or different and are

a) H,

b) phenyl,

c) C₁₋₆ alkyl, or

d) benzyl;

R₉₄ and R₉₅ at each occurrence are the same or different and are

a) H,

b) OH,

c) C₁₋₆ alkyl optionally substituted with —NR₈₃ R₈₄, or

d) R₉₄ and R₉₅ taken together are ═O;

R₉₆ is

a) an aromatic moiety having 6 to 10 carbon atoms,

b) a 5-, or 6-membered aromatic optionally benzo-fused heterocyclicmoiety having one to three atoms selected from the group consisting ofS, N, and O, wherein the substituents (a) and (b) which can in turn besubstituted with one or three —NO₂, CF₃, halo, —CN, OH, phenyl, C₁₋₅alkyl, C₁₋₅ alkoxy, or C₁₋₅ acyl,

c) morpholinyl,

d) OH,

e) C₁₋₆ alkoxy,

f) —NR₈₃R₈₄,

g) —C(═O)—R₉₇, or

R₉₇ is

a) morpholinyl,

b) OH, or

c) C₁₋₆ alkoxy;

h is 1, 2, or 3;

i is 0, 1, or 2;

j is 0 or 1;

k is 3, 4, or 5;

l is 2 or 3;

m is 4 or 5;

n is 0, 1, 2, 3, 4, or 5;

p is 0, 1, 2, 3, 4, or 5; with the proviso that n and p together are 1,2, 3, 4, or 5;

q is 1, 2, 3, or 4;

r is 2, 3, or 4;

t is 0, 1, 2, 3, 4, 5, or 6;

u is 1 or 2;

w is 0, 1,2, or 3.

DETAILED DESCRIPTION OF THE INVENTION

The new compounds of the invention can be prepared using known compoundsand intermediates of oxzolidinones, isoxazolines and butyolactones asintermediates and synthetic methods known in the art. Thioamides of theinvention can typically be prepared by the reaction of the correspondingamide with Lawesson's reagent.

Compounds disclosed in the following publications are suitableintermediates for preparation of the compounds of this invention and arehereby incorporated by reference for their disclosure of suitablecompounds that can be converted to the subject thiocarbonyl derivatives.

U.S. Pat. Nos. 5,225,565; 5,182,403; 5,164,510; 5,247,090; 5,231,188;5,565,571; 5,547,950; and 5,523,403.

PCT Application and publications PCT/US93/04850, WO94/01110;PCT/US94/08904, WO95/07271; PCT/US95/02972, WO95/25106; PCT/US95/10992,WO96/13502; PCT/US96/05202, WO96/35691; PCT/US96/12766; PCT/US96/13726;PCT/US96/14135; PCT/US96/17120; PCT/US96/19149; PCT/US97/01970;PCT/US95/12751, WO96/15130; and PCT/US96/00718, WO96/23788.

Chemical conversion techniques for converting various intermediateshaving a CH₂NH₂ on the oxazolidinone ring to CH₂NH—C(S)—CH₃ is disclosedby Hartke, K, Barrmeyer, S., J. prakt. Chem. 1996, 338, 251-6.Similarly, conversion of CH₂NHC(═O)CH₃ to CH₂NHC(S)NHCH₃ is reported byCava, M. P.; Levinson, M. I., Thionation Reactions of Lawesson'sReagents, Tetrahedron 1985, 41, 5061-87.

For the purpose of the present invention, the carbon content of varioushydrocarbon containing moieties is indicated by a prefix designating theminimum and maximum number of carbon atoms in the moiety, i.e., theprefix C_(i-j) defines the number of carbon atoms present from theinteger “i” to the integer “j”, inclusive. Thus, C₁₋₄ alkyl refers toalkyl of 1-4 carbon atoms, inclusive, or methyl, ethyl, propyl, butyland isomeric forms thereof.

The terms “C₁₋₂ alkyl”, “C₁₋₃ alkyl, “C₁₋₄ alkyl”, “C₁₋₅ alkyl”, “C₁₋₆alkyl”, “C₁₋₈ alkyl”, and “C₁₋₆ alkyl” refer to an alkyl group havingone to two, one to three, one to four, one to five, one to six, one toeight, or one to sixteen carbon atoms respectively such as, for example,methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl,decyl, undecyl, dodecyl, tridecyl, tetradecyl and their isomeric formsthereof.

The terms “C₂₋₄ alkenyl”, “C₂₋₅ alkenyl”, “C₂₋₈ alkenyl”, C₂₋₁₄ alkenyl”and “C₂₋₁₆ alkenyl” refer to at least one double bond alkenyl grouphaving two to four, two to five, two to eight, two to fourteen, or twoto sixteen carbon atoms, respectively such as, for example, ethenyl,propenyl, butenyl, pentenyl, pentdienyl, hexenyl, hexdienyl, heptenyl,heptdienyl, octenyl, octdienyl, octatrienyl, nonenyl, nonedienyl,nonatrienyl, undecenyl, undecdienyl, dodecenyl, tridecenyl, tetradecenyland their isomeric forms thereof.

The terms “C₂₋₅ alkynyl”, “C₂₋₈ alkynyl”, and “C₂₋₁₀ alkynyl” refer toat least one triple bond alkynyl group having two to five, two to eight,or two to ten carbon atoms respectively such as, for example, ethynyl,propynyl, butynyl, pentynyl, pentdiynyl, hexynyl, hexdiynyl, heptynyl,heptdiynyl, octynyl, octdiynyl, octatriynyl, nonynyl, nonediynyl,nonatriynyl and their isomeric forms thereof.

The terms “C₃₋₄ cycloalkyl”, “C₃₋₆ cycloalkyl”, “C₅₋₆ cycloalkyl”, and“C₃₋₈ cycloalkyl” refer to a cycloalkyl having three to four, three tosix, five to six, or threE to eight carbon atoms respectively such as,for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cycloheptyl, cyclooctyl, and their isomeric forms thereof.

The terms “C₁₋₄ alkoxy”, “C₁₋₆ alkoxy”, and “C₁₋₈ alkoxy” refer to analkyl group having one to four, one to six, or one to eight carbon atomsrespectively attached to an oxygen atom such as, for example, methoxy,ethoxy, propyloxy, butyloxy, pentyloxy, hexyloxy, heptyloxy, or octyloxyand their isomeric forms thereof The terms “C₁₋₆ alkylamino”, and “C₁₋₈alkylamino” refer to an alkyl group having one to six, or one to eightcarbon atoms respectively attached to an amino moiety such as, forexample, methylamino, ethylamino, propylamino, butylamino, pentylamino,hexylamino, heptylamino, or octoylamino and their isomeric formsthereof.

The terms “C₁₋₆ dialkylamino”, and “C₁₋₈ dialkylamino” refer to twoalkyl groups having one to six, or one to eight carbon atomsrespectively attached to an amino moiety such as, for example,dimethylamino, methylethylamino, diethylamino, dipropylamino,methypropylamino, ethylpropylamino, dibutylamino, dipentylamino,dihexylamino, methylhecylamino, diheptylamino, or dioctoylamino andtheir isomeric forms thereof

The terms “C₁₋₃ acyl”, “C₁₋₄ acyl”, “C₁₋₅ acyl”, “C₁₋₆ acyl”, “C₁₋₈acyl”, and “C₂₋₈ acyl” refer to a carbonyl group having an alkyl groupof one to three, one to four, one to five, one to six, one to eight, ortwo to eight carbon atoms.

The terms “C₁₋₄ alkoxyearbonyl”, “C₁₋₆ alkoxyearbonyl”, and “C₁₋₈alkoxycarbonyl” refer to an ester group having an alkyl group of one tofour, one to six, or one to eight carbon atoms.

The term “C₁₋₈ alkyl phenyl” refers to an alkyl group having one toeight carbon atoms and isomeric forms thereof which is substituted withat least one phenyl radical.

The term “C₂₋₈ alkenyl phenyl” refers to a at least one double bondalkenyl group having one to eight carbon atoms and isomeric formsthereof which is substituted with at least one phenyl radical.

The term “C₁₋₈ alkyl pyridyl” refers to an alkyl group having one toeight carbon atoms and isomeric forms thereof which is substituted withat least one pyridyl radical.

The term “C₁₋₈ hydroxyl” refers to an alkyl group having one to eightcarbon atoms and isomeric forms thereof attached to a hydroxy group.

The term “C₁₋₈ alkylsulfonyl” refers to an alkyl group having one toeight carbon atoms and isomeric forms thereof attached to a SO₂ moiety.

The term “C₁₋₆ alkylthio” refers to an alkyl group having one to sixcarbon atoms and isomeric forms thereof attached to a sulfur atom.

The term “Het” refers to 5 to 10 membered saturated, unsaturated oraromatic heterocyclic rings containing one or more oxygen, nitrogen, andsulfur forming such groups as, for example, pyridine, thiophene, furan,pyrazoline, pyrimidine, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl,4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, 3-pyrazinyl,2-quinolyl, 3-quinolyl, 1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl,2-quinazolinyl, 4-quinazolinyl, 2-quinoxalinyl, 1-phthalazinyl,4-oxo-2-imidazolyl, 2-imidazolyl, 4-imidazolyl, 3-isoxazolyl,4-isoxazolyl, 5-isoxazolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl,2-oxazolyl, 4-oxazolyl, 4-oxo-2-oxazolyl, 5-oxazolyl,4,5,-dihydrooxazole, 1,2,3-oxathiole, 1,2,3-oxadiazole,1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, 2-thiazolyl,4-thiazolyl, 5-thiazolyl, 3-isothiazole, 4-isothiazole, 5-isothiazole,2-indolyl, 3-indolyl, 3-indazolyl, 2-benzoxazolyl, 2-benzothiazolyl,2-benzimidazolyl, 2-benzofuranyl, 3-benzofuranyl, benzoisothiazole,benzisoxazole, 2-furanyl, 3-furanyl, 2-thienyl, 3-thienyl, 2-pyrrolyl,3-pyrrolyl, 3-isopyrrolyl, 4-isopyrrolyl, 5-isopyrrolyl,1,2,3,-oxathiazole-1-oxide, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl,5-oxo-1,2,4-oxadiazol-3-yl, 1,2,4-thiadiazol-3-yl,1,2,4-thiadiazol-5-yl, 3-oxo-1,2,4-thiadiazol-5-yl,1,3,4-thiadiazol-5-yl, 2-oxo-1,3,4-thiadiazol-5-yl, 1,2,4-triazol-3-yl,1,2,4-triazol-5-yl, 1,2,3,4-tetrazol-5-yl, 5-oxazolyl, 1-pyrrolyl,1-pyrazolyl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, 1-tetrazolyl,1-indolyl, 1-indazolyl, 2-isoindolyl, 7-oxo-2-isoindolyl,1-purinyl,3-isothiazolyl, 4-isothiazolyl and 5-isothiazolyl, 1,3,4,-oxadiazole,4-oxo-2-thiazolinyl, or 5-methyl-1,3,4-thiadiazol-2-yl, thiazoledione,1,2,3,4-thiatriazole, 1,2,4-dithiazolone. Each of these moieties may besubstituted as appropriate.

The term halo refers to fluoro, chloro, bromo, or iodo.

The compounds of the present invention can be converted to their salts,where appropriate, according to conventional methods.

The term “pharmaceutically acceptable salts” refers to acid additionsalts useful for administering the compounds of this invention andinclude hydrochloride, hydrobromide, hydroiodide, sulfate, phosphate,acetate, propionate, lactate, mesylate, maleate, malate, succinate,tartrate, citric acid, 2-hydroxyethyl sulfonate, fumarate and the like.These salts may be in hydrated form.

When Q is the structure of

the dotted line in the heterocyclic ring means that this bond can beeither single or double. In the case where the dotted line is a doublebond, the R₃₉ group will not be present.

The compounds of Formula I of this invention contain a chiral center atC5 of the isoxazoline ring, and as such there exist two enantiomers or aracemic mixture of both. This invention relates to both the enantiomers,as well as mixtures containing both the isomers. In addition, dependingon substituents, additional chiral centers and other isomeric forms maybe present in any of A or R₁ group, and this invention embraces allpossible stereoisomers and geometric forms in these groups.

The compounds of this invention are useful for treatment of microbialinfections in humans and other warm blooded animals, under bothparenteral and oral administration.

The pharmaceutical compositions of this invention may be prepared bycombining the compounds of this invention with a solid or liquidpharmaceutically acceptable carrier and, optionally, withpharmaceutically acceptable adjuvants and excipients employing standardand conventional techniques. Solid form compositions include powders,tablets, dispersible granules, capsules, cachets and suppositories. Asolid carrier can be at least one substance which may also function as adiluent, flavoring agent, solubilizer, lubricant, suspending agent,binder, tablet disintegrating agent, and encapsulating agent. Inertsolid carriers include magnesium carbonate, magnesium stearate, talc,sugar, lactose, pectin, dextrin, starch, gelatin, cellulosic materials,low melting wax, cocoa butter, and the like. Liquid form compositionsinclude solutions, suspensions and emulsions. For example, there may beprovided solutions of the compounds of this invention dissolved in waterand water-propylene glycol and water-polyethylene glycol systems,optionally containing suitable conventional coloring agents, flavoringagents, stabilizers and thickening agents.

Preferably, the pharmaceutical composition is provided employingconventional techniques in unit dosage form containing effective orappropriate amounts of the active component, that is, the compoundaccording to this invention.

The quantity of active component, that is the compound according to thisinvention, in the pharmaceutical composition and unit dosage formthereof may be varied or adjusted widely depending upon the particularapplication, the potency of the particular compound, the desiredconcentration. Generally, the quantity of active component will rangebetween 0.5% to 90% by weight of the composition.

In therapeutic use for treating, or combatting, bacterial infections inwarm-blooded animals, the compounds or pharmaceutical compositionsthereof will be administered orally, parenterally and/or topically at adosage to obtain and maintair a concentration, that is, an amount, orblood-level of active component in the animal undergoing treatment whichwill be antibacterially effective. Generally, such antibacteriallyeffective amount of dosage of active component will be in the range ofabout 0.1 to about 100, more preferably about 3.0 to about 50 mg/kg ofbody weight/day. It is to be understood that the dosages may varydepending upon the requirements of the patient, the severity of thebacterial infection being treated, and the particular compound beingused. Also, it is to be understood that the initial dosage administeredmay be increased beyond the above upper level in order to rapidlyachieve the desired blood-level or the initial dosage may be smallerthan the optimum and the daily dosage may be progressively increasedduring the course of treatment depending on the particular situation. Ifdesired, the daily dose may also be divided into multiple doses foradministration, e.g., 2-4 four times per day.

When the compounds according to this invention are administeredparenterally, i.e., by injection, for example, by intravenous injectionor by other parenteral routes of administration. Pharmaceuticalcompositions for parenteral administration will generally contain apharmaceutically acceptable amount of the compound or a soluble salt(acid addition salt or base salt) dissolved in a pharmaceuticallyacceptable liquid carrier such as, for example, water-for-injection anda buffer to provide a suitably buffered isotonic solution, for example,having a pH of about 3.5-6. Suitable buffering agents include, forexample, trisodium orthophosphate, sodium bicarbonate, sodium citrate,N-methylglucamine, L(+)-lysine and L(+)-arginine to name but a fewrepresentative buffering agents. The compound of this inventiongenerally will be dissolved in the carrier in an amount sufficient toprovide a pharmaceutically acceptable injectable concentration in therange of about 1 mg/mL to about 400 mg/mL of solution. The resultingliquid pharmaceutical composition will be administered so as to obtainthe above-mentioned antibacterially effective amount of dosage. Thecompounds according to this invention are advantageously administeredorally in solid and liquid dosage forms.

As a topical treatment an effective amount of Formula I is admixed in apharmaceutically acceptable gel or cream vehicle that can be applied tothe patient's skin at the area of treatment. Preparation of such creamsand gels is well known in the art and can include penetration enhancers.

MIC Test Method

The in vitro MICs of test compounds were determined by a standard agardilution method. A stock drug solution of each analog is prepared in thepreferred solvent, usually DMSO:H₂O (1:3). Serial 2-fold dilutions ofeach sample are made using 1.0 ml aliquots of sterile distilled water.To each 1.0 ml aliquot of drug is added 9 ml of molten Mueller Hintonagar medium. The drug-supplemented agar is mixed, poured into 15×100 mmpetri dishes, and allowed to solidify and dry prior to inoculation.

Vials of each of the test organisms are maintained frozen in the vaporphase of a liquid nitrogen freezer. Test cultures are grown overnight at35° C. on the medium appropriate for the organism. Colonies areharvested with a sterile swab, and cell suspensions are prepared inTrypticase Soy broth (TSB) to equal the turbidity of a 0.5 McFarlandstandard. A 1:20 dilution of each suspension is made in TSB. The platescontaining the drug supplemented agar are inoculated with a 0.001 mldrop of the cell suspension using a Steers replicator, yieldingapproximately 10⁴ to 10⁵ cells per spot. The plates are incubatedovernight at 35° C.

Following incubation the Minimum Inhibitory Concentration (MIC μg/ml),the lowest concentration of drug that inhibits visible growth of theorganism, is read and recorded. The data is shown in Tables I and II.

TABLE 1 Oxazolidinone MIC Values (Gram+) SAUR SEPI EFAE SPNE SPYOStructure 9213 12084 9217 9912 152 Comparison* 16 4 8 .5 1

Example 3 4 1 2 .25 .5

Comparison* 2 1 2 .5 1

Example 1 1 .25 .5 .13 .13

Example 5 1 .25 .5 <.125 .25

Example 6 2 1 2 .5 1

Comparison* .5 .25 1 .13 .25

Example 2 8 2 4 2 4

SAUR: S. aureus SEPI: S. epidermidis EFAE: E. faecalis SPNE: S.pneumoniae SPYO: S. pyogenes *not a compound of the subject invention

TABLE II Example SAUR SEPI EFAE SPNE SPYO HINF MCAT EFAE No. 9213 MIC30593 MIC 12712 MIC 9912 MIC 152 MIC 30063 MIC 30610 MIC 9217 MIC  1 10.25 0.5 <0.125 <0.125 8 1 0.5  2 8 4 8 2 4 >16 >16 4  3 4 1 1 0.25 0.516 4 2  5 1 0.5 0.5 <0.125 0.25 4 2 0.5  6 2 2 2 0.5 1 16 8 2  7 0.50.25 0.5 <0.125 0.25 4 1 0.5  8 2 1 0.5 <0.125 0.25 4 2 1  9 0.5 0.250.25 <0.125 <0.125 2 0.5 0.25 10 2 1 0.5 <0.125 0.25 2 1 1 11 0.25 0.250.25 <0.125 0.25 2 1 0.25 12 1 0.5 0.25 <0.125 <0.125 1 0.5 0.5 13 1 1 20.5 1 >16 8 2 14 1 0.5 1 0.25 0.5 8 1 1 15 32 16 32 4 8 >64 64 32 16 8 816 2 8 >64 32 16 17 2 2 4 1 2 64 16 4 18 2 1 2 <0.5 1 32 4 2 19 32 16 3216 16 64 32 32 21 4 4 8 2 4 64 16 8 22, 23 0.5 0.5 1 <0.125 0.25 4 2 124 1 0.25 0.5 <0.125 0.25 4 2 0.5 25 0.5 0.25 0.5 <0.125 <0.125 2 2 0.526 1 0.5 1 0.25 0.5 16 2 1 27 0.5 0.5 0.5 <0.125 0.25 4 2 1 28 0.5 0.250.5 0.25 0.25 2 1 0.5 29 0.25 0.25 0.25 <0.125 <0.125 2 0.5 0.25 30 4 10.5 <0.125 0.25 8 2 1 31 2 1 1 <0.125 0.25 4 1 1 32 16 2 2 0.25 0.25 8 24 33 4 2 1 0.25 0.25 4 2 4 34 2 1 2 0.5 1 >16 4 2 35 1 0.5 1 0.25 0.5 162 1 Key: SAUR  9213: S. aureus SEPI 30593: S. epidermidis EFAE 12712: E.Faecium SPNE  9912: S. pneumoniae SPYO  152: S. pyogenes HINF 30063:Haemophilus influenzae MCAT 30610: Moraxella catarrhalis EFAE  9217:Enterococcus faecalis

As shown in Scheme 1, the intermediates II for the compounds of thisinvention are also intermediates disclosed in the oxazolidinone patentsand published applications hereinabove incorporated by reference. Theintermediates IV for this invention are final products (Examples) fromthe oxazolidinone patents and published applications hereinaboveincorporated by reference.

As shown in Scheme 1, Step 1, and illustrated in Example 5, theisothiocyanates III can be conveniently prepared by allowing the amineintermediates (II) to react with 1,1′-thiocarbonyldi-2(1H)-pyridone insolvents such as methylene chloride at 0 to 25° C. The thioureas (Ia,R′=H, alkyl₁₋₄) can then be prepared as shown in Step 2 by the reactionof III with ammonia or the appropriate primary amines in solvents suchas 1,4-dioxane or tetrahydrofuran at 0-50° C. Alternatively, asillustrated in Example 6 and shown in Step 3, the thioureas can beprepared by allowing II to react with an appropriate isothiocyanate(R′—N═C═S) in solvents such as tetrahydrofuran at 0-50° C. Thioamides(Ib, R″=H, alkyl₁₋₄) are prepared by allowing II to react with anappropriate dithioester (R′″S—C(═S)—R″, Step 4 as illustrated in Example4. This reaction is carried out in aqueous-alcoholic solvents at 0-50°C. in the presence of an equivalent of an alkali metal hydroxide. Thisreaction, especially when R′″ is methyl or ethyl, can be catalyzed by analkali metal fluoride.

The reaction of II with R′″—S—C(S)—R′″ (R′″═CH₃, C₂H₅) to give Ib (Step4) can also be carried out in the presence of a tertiary amine base suchas triethylamine in solvents such as THF, dioxane or methylene chlorideat 10-50° C. for 3-48 hr.

When the reaction conditions are tolerated by the substituents on R(see, for example, Examples 1-3) the thioamides (Ib, R″—H, alkyl₁₋₄) canalso be conveniently prepared (Step 5) by allowing the appropriate amideintermediates (IV) to react with reagents such as2,4-bis(p-methoxyphenyl)-1,3-dithiadiphosphetane-2,4-disulfide(Lawesson's Reagent) in 1,4dioxane, benzene, toluene or tetrahydrofuranat 60-110° C.; phosphorus decasulfide and sodium carbonate intetrahydrofuran at 20-50° C. [Brillon, D., Synthetic Communications, 20,3085 (1990)] or phosphorus decasulfide and sodium fluoride in1,2-dimethoxyethane at 20-50° C. [Hartke, K, Gerber, H.-D., J. Prakt.Chem., 338, 763 (1996)].

Compounds Ic are prepared (Step 6) by allowing II to react first withcarbon disulfide and a tertiary amine base such as triethylamine insolvent mixtures containing water and methanol, ethanol or isopropanolat 10-50° C. for 5-24 hours. The resulting intermediate is treated withan alkylating agent (R″″ X where X represents bromo, iodo,alkylsulfonyloxy or arylsulfonyloxy) at 0-30° C. to give compounds Ic.In Step 7, compounds Ic are allowed to react with alkali metal alkoxidesuch as sodium methoxide or potassium ethoxide in the correspondingalkanol as solvent. This reaction is conveniently carried out at thereflux temperature of the alkanol for 1-24 hr.

In order to more fully illustrate the nature of the invention and themanner of practicing the same, the following experimental examples arepresented.

EXAMPLE 1(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide(I)

A stirred mixture of II (PCT/US94/08904, 3.37 g, 10.0 mmol) in drydioxane (100 mL), under nitrogen was treated with Lawesson's Reagent(4.04 g, 10.0 mml), warmed to reflux during 1 h and refluxed for 1.5 h.The reaction was complete by TLC on silica gel with 10% MeOH—CHCl₃. Itwas kept at ambient temperature for 18 h and concentrated in vacuo.Chromatography of the residue on silica gel with mixtures ofacetone-methylene chloride containing 10-15% acetone gave the productwhich was crystallized from acetone-hexane to give 1: mp 157.5-158.5°C.; HRMS theory for C₁₆H₂₀FN₃O₃S (M⁺): 353.1209; found: 353.1212. Anal.calcd for C₁₆H₂₀FN₃O₃S: C, 54.38; H, 5.38; N, 11.89; S, 9.07. Found: C,54.21; H, 5.58; N, 11.78; S, 8.93.

EXAMPLE 2(S)-N-[[3-[3-Fluoro-4-[4-(5-methyl-1,3,4-thiadiazol-2-yl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide(2)

According to Eiample 1, for the preparation of 1, 21 (PCT/US97/01970)was allowed to react with Lawesson's Reagent in refluxing dioxane togive 2: mp 222-223° C.; HRMS theory for C₁₉H₂₄FN₆O₂S₂ (M+H⁺): 451.1386;found 451.1381.

EXAMPLE 3(S)-N-[[3-[3-Fluoro-4-[2′,5′-dioxospiro[piperidine-4,4′-imidazolidine]-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide(3)

STEP A:(S)-N-[[3-[3-Fluoro-4-[2′,5′-dioxospiro[piperidine-4,4′-imidazolidine]-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide(32).

A stirred suspension of 31 (WO95/25106, 0.349 g, 1.00 mmol) in 1:1EtOH:H₂O (5 mL), under nitrogen, was treated with potassium cyanide(0.130 g, 2.00 mmol) and ammlonium carbonate (0.701 g, 7.30 mmol),warmed at 55-60° C. for 5 h 15 min and kept at ambient temperature for17 h 15 min. It was then chromatographed on silica gel with miiitures ofMeOH—NH₄OH—GHCl₃ containing 5-20% MeOH and 0.5% NH₄OH to give 0.280 g of32: HRMS caled for C₁₉H₂₂FN₅O₅: 419.1605 (M⁺); found 419.1613; Anal.caled for C₁₉H₂₂FN₅O₅. 1 H₂O: C, 52.17; H. 5.53; N. 16.01. Found: C,52.44; H, 5.30; N. 16.11.

STEP B:(S)-N-[[3-[3-Fluoro-4-[2′,5′-dioxospiro[piperidine-4,4′-imidazolidine]-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide(3).

A stirred suspension of 32 (0.210 g, 0.500 mmol) in dioxane (5.0 mL),under nitrogen was treated with Lawesson's Reagent (0.202 g, 0.500mmol), refluxed for 4 h and concentrated in vacuo. The residue waschromatographed on silica gel with mixctures of MeOH—NH₄OH—CHCl₃containing 1-10% MeOH and 0.1-0.5% NH₄OH and the resulting product wascrystallized from MeOH—CHCl₃—EtOAc to give 0.0491 g of 3: mip 218.5° C.;HR FAB MS theory for C₁₉H₂₂FN₅O₄S (M⁺): 435.1376; found 435.1370. Anal.calcd for C₁₉H₂₂FN₅O₄S. 0.5 H₂O: C, 51.34; H, 5.21; N. 15.76. Found: C,51.69; H, 5.00; N, 15.25.

EXAMPLE 4(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide(4)

A solution of 41 (148 mg, 0.500 mmol) and 0.97 M KOH (0.515 mL) inabsolute EtOH (5 mL) was added to a solution of ethyl dithioacetate (57μL, 0.50 mmol) and sodium fluoride (20 mg, 0.47 mmol) in absolute EtOH(5 mL) and the mixture was kept at ambient temperature for 3 h 40 min.Additional ethyl dithioacetate (5 μL) was added after 1 h 55 min andadditional 0.97 M KOH (40 mL) and sodium fluoride (6 mg) were added tothe mixture after 3h 5 min. The reaction was followed by TLC on silicagel with 10% MeOH—CHCl₃ and 30% acetone-CH₂Cl₂. The major product had anR_(f) on TLC that was the same as that of 4.

EXAMPLE 5(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea(5)

A solution of 51 (PCT/US94/08904, 2.07 g, 7.00 mmol) in CH₂Cl₂ wasadded, dropwise during 30 min, under nitrogen to an ice cold, stirredsolution of 1,1 ′-thiocarbonyldi-2(1H)-pyridone (1.95 g, 8.40 mmol) inCH₂Cl₂ (70 mL). The mixture was warmed slowly to ambient temperature andkept for 18 h. It was then diluted with CH₂Cl₂, washed with water andaqueous NaCl, dried (Na₂SO₄) and concentrated. Chromatography of theresidue on silica gel with 10% acetonitrile-CH₂Cl₂ gave 1.60 g of theisothiocyanate: HRMS theory for C₁₅H₁₆FN₃O₃S (M⁺): 337.0896; found337.0888.

Anhydrous ammonia was bubbled for 7 min through a stirred solution ofthe product from Step I (1.00 g, 2.96 mmol) in [HF (10 mL) and themixture was k ep t at ambient temperature for 3 h 25 min andconcentrated in vacuo. Crystallization of the residue fromacetone-hexane gave 0.861 g of 5: mp 199-199.5° C.; MS m/z 354 (M⁺).Anal. calcd for C₁₅H₁₉FN₄O₃S: C, 50.84; H, 5.40; N, 15.81. Found: C,50.87; H, 5.39; N, 15.72.

EXAMPLE 6(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′-methylthiourea(6)

A stirred solution of methyl isothiocyanate (93 mg, 1.27 mmol) in THF,was treated with 61 (295 mg, 1.00 mmol), kept at ambient temperature for18 h and concentrated in vacuo. The residue was recrystallized fromEtOAc-hexane to give 246 mg of 6: mp 158-160° C.; MS m/z 368 (M⁺). Anal.caled for C₁₆H₂₁FN₄O₃S: C, 52.16; H, 5.74; N, 15.21. Found: C, 52.20; H,5.85; N, 15.17.

EXAMPLE 7(S)-cis-N-[[3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]ethanethioamide

Step 1: A mixture of(S)-(−)-N-[[3-[3-fluoro-4-(3,6-dihydro-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamideS-oxide (4.50 g, can be obtained according to the procedures disclosedin International Publication No. WO 97/09328) and platinum oxide (697mg) in methanol (164 mL) is shaken on the Parr apparatus under ahydrogen atmosphere at 40 psi for 18 hours. The catalyst is then removedby filtration through Celite, and the filtrate is concentrated underreduced pressure and the residue chromatographed on silica gel (230-400mesh, 350 g), eluting with a gradient of methanol/methylene chloride(3/97-7/93). Pooling and concentration of those fractions with anR_(f)=0.44 by TLC (methanol/chloroform, 10/90) gives(S)-cis-)-N-[[3-[3-Fluoro-4-(tetrahydro-1-oxddo-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide,mp 203-204° C.

Step 2: A mixture of the compound prepared in Step 1 (2.50 g) andhydroxylamine hydrochloride (2.36 g) in pyridine (30.6 mL) and ethanol(3.4 mL) is stirred in a screw-cap vial at 100° C. for 22 hrs and atambient temperature for 16 hrs, during which additional hydroxylaminehydrochloride (944 mg) and pyridine (4 mL) is added. The reactionmixture is then concentrated under reduced pressure, diluted withsaturated aqueous sodium bicarbonate (100 mL) and saline (50 mL),adjusted to pH 11 with solid sodium carbonate and extracted withmethanol/methylene chloride (10/90, 5×100 mL). The combined organicphase is concentrated under reduced pressure, and the crude product ischromatographed on silica gel (230-400 mesh, 150 g), eluting with agradient of methanol/methylene chloride (6/94-10/90). Pooling andconcentration of those fractions with an R_(f)=0.14 by TLC(methanol/chloroform, 10/90) gives(S)-cis-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone,mp 159-161° C.

Step 3: A solution of ethyl dithioacetate (105 mL, 0.919 mmol) andsodium fluoride (39 mg, 0.919 mmol) in ethanol (9.2 mL) under a nitrogenatmosphere was treated with a mixture of(S)-cis-3-[3-fluoro4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone,as prepared in Step 2,(300 mg, 0.919 mmol) and aqueous potassiumhydroxide (1M, 0.92 mL) in ethanol (46 mL). The resulting solution wasstirred at ambient temperature for 4 hours and was then diluted withmethylene chloride (150 mL) and washed with water (50 mL), aqueouspotassium hydrogen sulfate (1M, 50 mL) and brine (25 mL). The organicphase was dried over anhydrous sodium sulfate and concentrated in vacuo,and the crude product was triturated with methylene chloride/diethylether and filtered to give the title compound, mp 176-177° C. (dec.).

EXAMPLE 8(S)-cis-[[3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea

Step 1: A solution of 1,1′-thiocarbonyldi-2(1H)-pyridone (235 mg, 1.01mmol) in anhydrous methylene chloride (10 mL) at 0° C. under a nitrogenatmosphere was treated with a solution of(S)-cis-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran4-yl)phenyl]-5-aminomethyl-2-oxazolidinone,as prepared in Example 7, Step 2, (275 mg, 0.843 mmol) in anhydrousmethylene chloride (34 mL) over 30 minutes. The resulting mixture wasstirred at 0° C. for 30 minutes and at ambient temperature for 1 hourand was then diluted with methylene chloride (40 mL), washed with water(25 mL) and brine (25 mL), dried over anhydrous sodium sulfate andconcentrated in vacuo. The crude product was chromatographed on silicagel (70-230 mesh, 20 g), eluting with acetonitrile/methylene chloride(40/60), and those fractions with an R_(f)=0.07 by TLC(acetonitrile/methylene chloride, 30/70) were pooled and concentrated togive(S)-cis-3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-isothiocyanatomethyl-2-oxazolidinone,mp 187-190° C. (dec.).

Step 2: A solution of(S)-cis-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-isothiocyanatomethyl-2-oxazolidinone(Step 1, 290 mg, 0.787 mmol) in anhydrous tetrahydrofuran (39 mL) at 0°C. under a nitrogen atmosphere was treated (bubbled) with a stream ofammonia gas for 5 minutes. The reaction pot was sealed, and theresulting mixture was stirred at 0° C. for 1 hour. The excess ammoniawas then removed under a stream of nitrogen, and the reaction mixturewas concentrated in uacuo to give the crude product. Recrystallizationfrom methanol/methylene chloride/diethyl ether gave the title compound,mp 206-208° C. (dec.).

EXAMPLE 9(S)-trans-N-[[3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]ethanethioamide

Step 1:(S)-(−)-N-[[3-[3-fluoro-4-(3,6-dihydro-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide S-oxide (disclosed in InternationalPublication No. WO 97/09328) may be reduced to the corresponding cis-and trans-sulfoxides by catalytic hydrogenation in the presence of acatalyst and solvent. Alternatively, the sulfide by product of thisreduction reaction can be oxidized with an oxidizing agent such NaIO₄ ormeta-chloroperoxybenzoic acid in solvent to provide the cis- andtrans-sulfoxides. Alternatively, the sulfide byproduct acn be oxidizedselectively to the trans isomer using t-butyl hydroperoxide and acatalyst such as Ti(OiPr)4 and D-diisopropyl tartrate in a suitablesolvent. The isomeric mixture can then be separated by chromatography toisolate the trans-sulfoxide, mp 211-212° C. (dec.). A mixture of thetrans-sulfoxide,(S)trans-(−)-N-[[3-[3-fluoro-4-(tetrahydro-1-oido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide,(0.90 g) and hydroxylamine hydrochloride (0.85 g) in pyridine (11.0 mL)and ethanol (1.2 mL) is stirred in a screw-cap vial at 100° C. for 23hrs and at ambient temperature for 19 hrs, during which additionalhydroxylamine hydrochloride (340 mg) and pyridine (1 mL) is added. Thereaction mixture is then concentrated under reduced pressure, dilutedwith saturated aqueous sodium carbonate (50 mL) and saline (50 mL) andextracted with methanolmethylene chloride (10/90, 6×100 mL). Thecombined organic phase is concentrated under reduced pressure, and thecrude product is chromatographed on silica gel (230-400 mesh, 45 g),eluting with a gradient of methanol/methylene chloride (7.5/92.5-10/90).Pooling and concentration of those fractions with an R_(f=0.14) by TLC(methanol/chloroform, 10/90) gives(S)-trans-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-5oxazolidinone, mp 138-140° C.

Step 2: A solution of ethyl dithioacetate (105 mL, 0.919 mmol) andsodium fluoride (39 mg, 0.919 mmol) in ethanol (9.2 mL) under a nitrogenatmosphere was treated with a mixture of(S)-trans-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone,as prepare in Step 1, (300 mg, 0.919 mmol) and aqueous potassiumhydroxide (1M, 0.92 mL) in ethanol (46 mL). The resulting solution wasstirred at ambient temperature for 17 hours and was then diluted withmethylene chloride (150 mL), washed with water (2×50 mL) and brine (25mL), dried over anhydrous sodium sulfate and concentrated in vacuo. Thecrude product was chromatographed on silica gel (230-400 mesh, 35 g),eluting with methanol/methylene chloride (3/97), and those fractionswith an R_(f)=0.56 by TLC (methanolchloroform, 10/90) were pooled andconcentrated and the residue recrystallized from methylenechloride/diethyl ether to give the title compound, mp 193-194° C.(dec.).

EXAMPLE 10(S)-trans-[[3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea

Step 1: A solution of 1,1′-thiocarbonyldi-2(1H)-pyridone (192 mg, 0.827mmol) in anhydrous methylene chloride (8.3 mL) at 0° C. under a nitrogenatmosphere was treated with a solution of(S)-trans-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran4-yl)phenyl]-5-aminomethyl-2-oxazolidinone,as prepared in Example 9, Step 1, (225 mg, 0.689 mmol) in anhydrousmethylene chloride (28 mL) over 30 minutes. The resulting mixture wasstirred at 0° C. for 30 minutes and at ambient temperature for 40minutes and was then diluted with methylene chloride (20 mL), washedwith water (15 mL) and brine (15 mL), dried over anhydrous sodiumsulfate and concentrated in uacuo. The crude product was chromatographedon silica gel (32-63 mm, 40 g), eluting with a gradient ofacetonitrile/methylene chloride (30/70-60/40) under 15 psi N₂, and thosefractions with an R_(f)=0.12 by TLC (acetonitrile/methylene chloride,30/70) were pooled and concentrated to give(S)-trans-3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-isothiocyanatomethyl-2-oxazolidinone,mp 165-167° C.

Step 2: A solution of(S)-trans-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-isothiocyanatomethyl-2-oxazolidinone(Step 1, 230 mg, 0.624 mmol) in anhydrous tetrahydrofuran (31.2 mL) at0° C. under a nitrogen atmosphere was treated (bubbled) with a stream ofammonia gas for 5 minutes. The reaction pot was sealed, and theresulting mixture was stirred at 0° C. for 1 hour. The excess ammoniawas then removed under a stream of nitrogen, and the reaction mixturewas concentrated in vacuo to give the crude product. Trituration withmethanol/methylene chloride/diethyl ether gave the title compound, mp209-210° C. (dec.).

EXAMPLE 11(S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]ethanethioamide

Step 1: Starting with(S)-cis-(−)-N-[[3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamideas prepared in Example 7, Step 1, and following the general procedure ofStep 2, and making non-critical variations by substituting(S)-(−)-N-[[3-[3-fluoro-4-(tetrahydro-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamideS,S-dioxide (disclosed in International Publication No. WO 97/09328) for(S)cis-(−)-N-[[3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide,the product(S)-(−)-3-[3-Fluoro-4-(tetrahydro-1,1-dioxddo-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinoneis obtained, mp 194° C. (dec.).

Step 2: A solution of ethyl dithioacetate (100 mL, 0.876 mmol) andsodium fluoride (37 mg, 0.876 mmol) in ethanol (8.8 mL) under a nitrogenatmosphere was treated with a mixture of(S)-(−)-3-[3-fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone,as prepared in Step 1, (300 mg, 0.876 mmol) and aqueous potassiumhydroxide (1M, 0.88 mL) in ethanol (43.8 mL). The resulting mixture wasstirred at ambient temperature for 26 hours, during which additionalethyl dithioacetate (50 mL, 0.438 mmol), sodium fluoride (19 mg, 0.438mmol), aqueous potassium hydroxide (1M, 0.44 mL) and ethanol (3.0 mL)was added, and was then diluted with methylene chloride (150 mL), washedwith water (50 mL), aqueous potassium hydrogen sulfate (1M, 50 mL) andbrine (25 mL), dried over anhydrous sodium sulfate and concentrated invacuo. The crude product was recrystallized from methylenechlorideldiethyl ether to give the title compound, mp 186-187° C.(dec.).

EXAMPLE 12(S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea

Step 1: A solution of 1,1′-thiocarbonyldi-2(1H)-pyridone (304 mg, 1.31mmol) in anhydrous methylene chloride (13 mL) at 0° C. under a nitrogenatmosphere was treated with a solution of(S)-(−)-3-[3-fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone,as prepared in Example 11, Step 1, (375 mg, 1.09 mmol) in anhydrousmethylene chloride (88 mL) over 30 minutes. The resulting mixture wasstirred at 0° C. for 30 minutes and at ambient temperature for 30minutes and was then diluted with methylene chloride (40 mL), washedwith water (25 mL) and brine (25 mL), dried over anhydrous sodiumsulfate and concentrated in vacuo. The crude product was chromatographedon silica gel (230-400 mesh, 45 g), eluting with acetonitrile/methylenechloride (7.5/92.5), and those fractions with an R_(f)=0.64 by TLC(acetonitrile/methylene chloride, 20/80) were pooled and concentrated togive(S)-3-[3-fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-5-isothiocyanatomethyl-2-oxazolidinone,mp 158-162° C. (dec.).

Step 2: A solution of(S)-3-[3-fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-5-isothiocyanatomethyl-2-oxazolidinone(Step 1, 380 mg, 0.988 mmol) in anhydrous tetrahydrofuran (49 mL) at 0°C. under a nitrogen atmosphere was treated (bubbled) with a stream ofammonia gas for 5 minutes. The reaction pot was sealed, and theresulting mixture was stirred at 0° C. for 1 hour. The excess ammoniawas then removed under a stream of nitrogen, and the reaction mixturewas concentrated in vacuo to give the crude product. Recrystallizationfrom methanol/methylene chloride/diethyl ether gave the title compound,mp 196-198° C. (dec.).

EXAMPLE 13(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-thioformamide(7)

A stirred mixture of acetic anhydride (0.23 mL, 0.0024 mol) and 95-97%formic acid (0.10 mL, 0.0027 mL) was warmed, under nitrogen at 50-55° C.for 2 h, cooled to ambient temperature and treated, portionwise during 2min, with 39⁸ (0.45 g, 0.0015 mol). The suspension was kept at ambienttemperature for 4 h and the resulting solution was treated with Et2O (1mL) and kept at ambient temperature for 18 h. The mixture was dilutedwith additional Et₂O (10 mL) and the solid was collected by filtration,washed with Et₂O and dried to give 0.38 g of 6⁹: MS (ES) m/z 324 (M+H⁺),346 (M+Na⁺); ¹H NMR (300 mHz, CDCl₃) d 3.08 (m, 4H), 3.72 (m, 2H), 3.77(d,d, 1H), 3.89 (m, 4H), 4.04 (t, 1H), 4.80 (m, 1H), 6.33 (s, 1H), 7.05(m, 2H), 7.45 (d,d, 1H), 8.27 (s, 1H).

A stirred mixture of 6 (0.38 g, 0.00118 mol) in dioxane (20 mL), undernitrogen was treated with 4 (0.51 g, 0.00126 mol), warmed to refluxduring 30 min and kept at this temperature for 90 min. It was thenevaporated under a stream of nitrogen. The residue was chromatographedon silica gel with 1.25% MeOH—CH₂Cl₂ and the slightly impure product wasrechromatographed on silica gel with 25% EtOAc—CH₂Cl₂. The resultingproduct was crystallized from EtOAc-methyl tert-butyl ether to give0.114 g of 7: mp 150-155° C. (dec); IR (DRIFT) 3322, 1752 cm⁻¹; MS(ES)m/z 340 (M+H⁺), 362 (M+Na⁺); ¹HNMR [300 MHz, (CD₃)₂SO] d 2.94 (m, 4H),3.72 (m, 4H), 3.77 (d,d, 1H), 3.94 (t, 2H), 4.12 (t, 1H), 4.93 (m, 1H),7.05 (t, 1H), 7.16 (d,d, 1H), 7.47 (d,d, 1H), 9.33 (d, 1H), 10.59 (s,1H). Anal. calcd for C₁₅H₁₈FN₃O₃S: C, 53.08; H, 5.35; N, 12.38. Found:C, 53.02; H, 5.44; N, 12.36.

EXAMPLE 14(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiopropion-amide(9)

An ice cold, stirred solution of 39 (0.395 g, 0.00134 mol) and triethylamine (0.186 mL, 0.0027 mol) in CH₂Cl₂ (20 mL), under nitrogen wastreated, dropwise during 2 min, with a solution of propionyl chloride(0.128 mL, 0.00147 mol) in CH₂Cl₂ (3 mL). The mixture was kept in theice bath for 20 min and at ambient temperature for 1 h. It was thendiluted with CH₂Cl₂, washed with saturated NaHCO₃, water and brine,dried (MgSO₄) and concentrated. The residue (8) was used without furtherpurification in the next reaction.

A stirred mixture of the product (8) from the previous reaction anddioxane (20 mL), under nitrogen, was treated, portionwise during 1 min.with Lawesson's reagent (0.58 g, 0.0014 mol) and refluxed for 2 h; itwas then concentrated. The residue was chromatographed on silica gelwith 2% MeOH—CHCl₃ and the product was crystallized from methyltert-butyl ether to give 0.259 g of 9: mp 138-139° C.; MS(ES) m/z 368(M+H⁺), 390 (M+Na⁺); IR (DRIFT) 3284, 3266, 1748, 1744 cm⁻¹; [α]²⁴_(D)+20° (MeOH); 1H NMR[300 MHz, (CD₃)₂SO] d 1.12 (t, 3H), 2.56 (q, 2H),2.94 (m, 4H), 3.72 (m, 4H), 3.78 (d,d, 1H), 3.90 (t, 2H), 4.11 (t, 1H),4.93 (m, 1H), 7.05 (t, 1H), 7.16 (d,d, 1H), 7.47 (d,d, 1H), 10.30 (broads, 1H). Anal. caled for C₁₇H₂₂FN₃O₃S: C, 55.57; H, 6.03; N. 11.44.Found: C, 55.68; H. 6.21; N, 11.37.

EXAMPLE 15(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxrazolidinyl]methyl]-2-chlorotlioacetamide(11)

A stirred solution of 39 (1.54 g, 5.2 mmol) and triethylamine (750 mg,7.5 mmol) in CH₂Cl₂ (50 mL), urnder nitrogen, was treated, dropwise,during 15 min with a solution of chloroacetyl chloride (465 mL, 5.8mmol) in CH₂Cl₂ (30 mL) and kept at ambient temperature for 18 h. It wasthen washed with saturated NaHCO₃ and dilute NaCl, dried (Na₂SO₄) andconcentrated. The residue was flash chromatographed on silica gel with20-30% acetone-CH₂Cl₂ to give 1.49 g of 10⁹ which was used in the nextreaction without further purification.

A stirred mixture of 10 (0.371 g, 1.0 mmol) and Lawesson's reagent(0.420 mg, 1.04 mmol) in dioxane (10 mL) was refluxed, under nitrogenfor 2 h and concentrated under reduced pressure. The residue waschromatographed on silica gel with 3-10% acetone-CH₂Cl₂ to give 0.143 gof 11: MS (CI) m/z 388 (M+H⁺); ¹H NMR (300 MHz, CDCl₃) d 3.07 (m, 4H),3.77 (d,d, 1H), 3.88 (m, 4H), 4.04 (m, 1H), 4.12 (t, 1H), 4.35 (m, 1H),4.61 (s, 2H), 4.98 (m, 1H), 6.96 (t, 1H), 7.08 (d,d, 1H), 7.44 (d,d,1H), 8.69 (s, 1H). Anal. calcd for C₁₆H₁₉ClFN₃O₃S: C, 49.55; H, 4.94; N,10.83. Found: C, 49.38; H, 5.20; N, 10.27.

EXAMPLE 16(S)-N-[[3-[3-Fluoro-4-(4-moropholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α,α,α-trifluorothioacetamide(13)

An ice cold stirred solution of 39 (0.590 g, 2.0 mmol) and triethylamine(640 mL, 4.6 mmol) in CH₂Cl₂ (10 mL) was treated with trifluoroaceticanhydride (325 mL, 2.3 mmol) and kept in the ice bath for 10 min andthen at ambient temperature. The reaction was followed by TLC on silicagel with 30% acetone-CH₂Cl₂. Additional trifluoroacetic anhydride andtriethylamine were added after 3 d (64 mL/125 mL), 4 d (100 mL/220 mL)and 6 d (325 mL/1.0 mL). The reaction was complete 1 h after the lastaddition; it was mixed with CH₂Cl₂, washed with water and dilute NaCl,dried (Na₂SO₄) and concentrated. The solid residue was recrystallizedfrom acetone-heptane to give 0.566 g of 12: mp 161-164° C. (dec); MS(EI)m/z 391 (M⁺). Anal. calcd for C₁₆H₁₇F₄N₃O₄: C, 49.11; H, 4.38; N, 10.74.Found: C, 48.99; H, 4.56; N, 10.73.

A stirred ure of 12 (0.391 g, 1.0 mmol) and Lawesson's reagent (0.422 g,1.1 mmol) in dioxane (10 mL) was refluxed, under nitrogen for 2 h,cooled slowly to ambient temperature and concentrated in vacuo. Theresidue was flash chromatographed on silica gel with 5-15%acetone-CH₂Cl₂ and the product was crystallized from acetone-heptane togive 0.249 g of 13: mp 151-152° C.; MS(EI) m/z 407 (M⁺), 363, 209, 151,95; ¹H NMR (300 MHz, CDCl₃) d 3.05 (m, 4H), 3.75 (d,d, 1H), 3.87 (m,4H), 3.95 (m, 1H), 4.14 (t, 1H), 4.32 (m, 1H), 5.01 (m, 1H), 6.92 (t,1H), 7.05 (d,d, 1H), 7.38 (d,d, 1H), 9.03 (s, 1H). Anal. calcd forC₁₆H₁₇F₄N₃O₃S: C, 47.17; H, 4.21; N, 10.31. Found: C, 47.09; H, 4.35; N,10.27.

EXAMPLE 17(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α-fluorothioacetamide(15)

A stirred, ice cold solution of 39 (0.590 g, 2.0 mmol) andtriethylarnine (611 mL, 4.4 mmol) in CH₂Cl₂ (10 mL), under nitrogen, wastreated, dropwise, with a solution of fluoroacetyl chloride (220 mL, 2.2mmol) in CH₂Cl₂ (5 mL), kept in the ice bath for 10 min and at ambienttemperature for 2 h. It was then diluted with CH₂Cl₂, washed with waterand dilute NaCl, dried (Na₂SO₄) and concentrated. The residue waschromatographed on silica gel with 10-30% acetone-CH₂Cl₂ to give 0.180 gof 14: MS(ES) m/z 356 (M+H⁺), 378 (M+Na⁺).

A solution of 14 (0.180 g, 0.507 mmol) in dioxane, under nitrogen, wastreated with Lawesson's reagent (0.206 g, 0.51 mmol), warmed at 90-100°C. for 1 h and concentrated in vacuo. The residue was chromatographed onsilica gel with 15% acetone-CH₂Cl₂ to give 0.161 g of 15: MS(EI) m/z 371(M⁺); ¹H NMR (300 MHz, CDCl₃) d 3.05 (m, 4H), 3.78 (d,d, 1H), 3.87 (m,4H), 4.03 (m, 1H), 4.11 (t, 1H), 4.38 (m, 1H), 4.98 (m, 1H), 5.07 (s,1H), 5.23 (s, 1H), 6.93 (t, 1H), 7.08 (dd, 1H, 7.42 (d,d, 1H), 8.42 (s,1H). Anal. calcd for C₁₆H₁₉F₂N₃O₃S: C, 51.74; H, 5.16; N, 11.31. Found:C, 51.79; H, 5.31; N, 11.02.

EXAMPLE 18(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α,α-difluorothioacetamide(17)

A stirred, ice cold mixture of 39 (0.590 g, 2.0 mmol), difluroaceticacid (190 mL, 2.0 mmol), and 1-hydroxybenzotriazole (0.297 g, 2.2 mmol)in DMF (5 mL) under nitrogen, was treated with1-(3-dimethylaminopropyl)-3-ethylcarbonde hydrochloride (0.843 g, 4.4mmol) and kept at ambient temperature for 18 h. It was diluted withCH₂Cl₂, washed with water and dilute NaCl, dried (Na₂SO₄) andconcentrated. The solid residue was crystallized form EtOAc-heptane togive 0.617 g of 16: mp 149-150° C.; 1H NMR (300 MHz, CDCl3) d 3.05 (m,4H), 3.66 (m, 2H), 3.85 (m, 5H), 4.08 (t, 1H), 4.80 (m, 1H), 5.93 (t,J=53.9 Hz, 1H), 6.92 (t, 1H), 7.06 (m, 2H), 7.39 (d,d, 1H); MS(EI) m/z373 (M⁺). Anal. calcd for C₁₆H₁₈F₃N₃O₄: C, 51.48; H, 4.86; N, 11.26.Found: C, 51.59; H, 4.91; N, 11.29.

A stirred solution of 16 (0.373 g, 1.00 mmol) in dioxane (10 mL), undernitrogen was treated with Lawesson's reagent (0.404 g, 1.00 mmol),warmed at about 95° C. for 1 h and concentrated in vacuo. Chromatographyof the residue on silica gel with 10% acetone-CH₂Cl₂ and cyrstallizationof the product from EtOAc-heptane gave 0.276 g of 17: mp 125-127° C.;MS(EI) m/z 389 (M⁺), 345, 305, 247, 209, 195, 151, 138, 123, 109, 95; ¹HNMR (300 MHz, CDCl₃) d 3.05 (m, 4H), 3.76 (d,d, 1H), 3.86 (m, 4H), 4.01(m, 1H), 4.12 (t, 1H), 4.30 (m, 1H), 4.99 (m, 1H), 6.20 (t, J=55.9 Hz,1H), 6.92 (t, 1H), 7.06 (d,d, 1H), 7.38 (d,d, 1H), 8.78 (broad s, 1H).Anal. calcd for C₁₆H₁₈F₃N₃O₃S: C, 49.35; H, 4.66; N, 10.79. Found: C,49.37; H, 4.71; N, 10.83.

EXAMPLE 19 (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-10oxazolidinyl]methyl]-α-eyanothioacetamnide (19)

An ice cold, stirred mixture of 39 (0.646 g, 2.19 mmol), cyanoaceticacid (0.179 g, 2.1 mmol) and 1-hydroxybenzotriazole (0.351 g, 2.6 mmol)in DMF (5 mL, under nitrogen, was treated with1-(3-dimethylaminopropyl)-3-ethylcarbodiimnide hydrochloride (0.997 g,5.2 mmol) and kept at ambient temperature for 24 h. It was diluted withCH₂Cl₂, washed with water and dilute NaCl, dried (Na₂SO₄) andconcentrated. The solid residue was crystallized from EtOAc-heptane togive 0.546 g of 18: mp 172-174° C.: IR (DRIFT) 3316, 2256, 1754, 1684cm⁻¹; MS(EI) m/z 362 (M⁺). Anal. calcd for C₁₇H₁₉FN₄O₄: C, 56.35; H,5.28; N. 15.46. Found: C, 56.33; H, 5.30; N, 15.36.

A stirred solution of 18 (0.453 mg, 1.25 mmol) in dioxane (10 mL), undernitrogen, was treated with Lawesson's reagent (0.505 g, 1.25 mmol) andwarmed at about 100° C. When the reaction was over (TLC with 30%acetone-CH₂Cl₂) the mixture was cooled and concentrated in vacuo.Chromatography of the residue on silica gel with 10-20% acetone-CH₂Cl₂and crystallization of the product from EtOAc-heptane gave 0.110 g of19: mp 186-187° C. (dec); MS(ES) m/z 379 (M+H⁺), 401 (M+Na⁺); ¹H NMR(300 MHz, CDCl₃) d 3.05 (m, 4H), 3.81 (d,d, 1H), 3.86 (m, 4H), 3.89 (s,2H), 4.09 (t, 1H), 4.14 (m, 2H), 5.01 (m, 1H), 6.92 (t, 1H), 7.05 (d,d,1H), 7.34 (d,d, 1H), 9.15 (s, 1H); IR (DRIFT) 3244, 2260, 1754 cm⁻¹.Anal. calcd for C₁₇H₁₉FN₄O₃S: C, 53.96; H, 5.06; N, 14.81. Found: C,53.88; H, 5.39; N, 14.61.

EXAMPLE 20(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α,α-dichlorothioacetamide(21)

A stirred, ice cold solution of 39 (0.885 g, 3.00 mmol) andtriethylamine (975 mL, 7 mmol) in CH₂Cl₂ (15 mL), under nitrogen wastreated, dropwise with a solution of dichloroacetic anhydride (555 mL,3.5 mmol) in CH₂Cl₂ (5 mL) and kept in the ice bath for 15 min and atambient temperature for 18 h. It was diluted with CH₂Cl₂, washed withwater, saturated NaHCO₃ and dilute NaCl, dried (Na₂SO₄) andconcentrated. Chromatography of the residue on silica gel with 10%acetone-CH₂Cl₂ and crystallization of the product from acetone-heptanegave 0.463 g of 20: mp 197-198° C. (dec); MS(ES) m/z 406 (M+H⁺), 428(M+Na⁺); ¹H NMR (300 MHz, CDCl₃) d 3.05 (m, 4H), 3.75 (m, 3H), 3.86 (m,4H), 4.07 (t, 1H), 4.83 (m, 1H), 5.94 (s, 1H), 6.92 (t, 1H), 7.06 (m,2H), 7.41 (d,d, 1H).

A stirred solution of 20 (0.305g, 0.75 mmol) in dioxane (5 ml), undernitrogen, was treated with Lawesson's reagent (0.202g, 0.5 mmol), warmedat about 90° C. for 1 hour, cooled and concentrated in vacuo.Chromatography of the residue on silica gel first with 30%acetone-heptane and then with 10% acetone-methylene chloride andcrystallization of rh product form methylene chloride—heptane gave 0.203g with 21: mp 143-144° cd.; HR₁₇S (EI) calculated for C₁₆H₁₈cl₂ F N₃ O₃S(M) 421.0431. Anal. calcd for C₁₆H₁₈cl₂ F N₃ O₃ S, C, 45.51; H, 4.30;N, 9.95. Found: C, 45.47; H, 4.24; H, 9.88.

EXAMPLE 21(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α-(methoxycarbonyl)thioacetamide(23)

A stirred solution of 39 (0.955 g, 3.2 mmol) and triethylamine (650 mL,4.5 mmol) in CH₂Cl₂ (50 mL), under nitrogen, was treated, dropwiseduring 15-20 min with a solution of methyl malonyl chloride (475 mL, 4.3mmol) in CH₂Cl₂ (10 mL) and kept at ambient temperature for 3 days. Itwas then washed with water and dilute NaCl, dried and concentrated. Theresidue was flash chromatographed on silica gel with 15-30%acetone-CH₂Cl₂ and the product was crystallized form acetone-hexane togive 0.873 g of 22: mp 150-151° C.; ¹H NMR (300 MHz, CDCl₃) d 3.03 (m,4H), 3.34 (s, 2H), 3.67 (s, 3H), 3.69 (m, 2H), 3.76 (d,d, 1H), 3.85 (m,4H), 4.00 (t, 1H), 4.78 (m, 1H), 6.90 (t, 1H), 7.06 (d,d, 1H), 7.41(d,d, 1H), 7.57 (t, 1H); MS(ES) m/z 396 (M+H⁺), 418 (M+Na⁺); HRMS (FAB)calcd for C₁₈H₂₃FN₃O₆ (M+H⁺) 396.1571, found 396.1579. Anal. calcd forC₁₈H₂₂FN₃O₆: C, 54.68; H, 5.61; N, 10.63. Found: C, 54.69; H, 5.68; N,10.58.

A stirred solution of 22 (0.395 g, 1.0 mmol) in dioxane (10 mL), undernitrogen, was treated with Lawesson's reagent (0.202 g, 0.5 mmol) andkept at ambient temperature for 4 h 10 min and at 80-90° C. for 1.5 h.The reaction was followed by TLC on silica gel with 10% MeOH-CHCl₃. Atthis time a new, less polar product had begun to form. It was kept atambient temperature for 18 h and at 80° C. for 2 h; additionalLaewsson's reagent (40 mg, 0.099 mmol) was added and warming at 80° C.was continued for 2 h; some starting material still remained. Themixture was concentrated and the residue was chromatographed on silicagel with 15% acetone-CH₂Cl₂ to give 0.348 g of 23: ¹H NMR (300 MHz,CDCl₃) d 3.05 (m, 4H), 3.71 (s, 3H), 3.81 (d,d, 1H), 3.86 (m, 4H), 3.88(s, 2H), 4.07 (t, 1H), 4.19 (m, 2H), 4.99 (m, 1H), 6.91 (t, 1H), 7.07(d,d, 1H), 7.42 (d,d, 1H), 9.52 (s, 1H); IR (DRIFT) 3269, 1743 cm⁻¹;MS(EI) m/z 411 (M⁺). Anal. calcd for C₁₈H₂₂FN₃O₅S: C, 52.54; H, 5.39; N,10.21. Found: C, 52.58; H, 5.43; N, 10.14.

EXAMPLE 22(S)-N-[[3-[4-[1-[1,2,4]Triazolyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide(25)

A stirred mixture of 24 (0.150 g, 0.470 mmol) and dioxane (12.5 mL),under nitrogen, was treated with Lawesson's reagent (0.20 g, 0.50 mmol),refluxed for 1.5 h, kept at ambient temperature for 18 h andconcentrated in vacuo. Flash chromatography of the residue on silica gelwith 5% MeOH-CHCl₃ gave the product which was crystallized from MeOH togive 0.100 g (63.4%) of 25: mp 161-163° C.; ¹H NMR [300 MHz, (CD₃)₂SO] d2.43 (s, 3H), 3.87 (m, 3H), 4.22 (t, 1H), 4.99 (m, 1H), 7.51 (d, 1H),7.77 (m, 2H), 8.26 (s, 1H), 8.97 (d, 1H), 10.35 (broad s, 1H); IR (mull)3259, 3226, 3044, 1752 cm⁻¹; MS(ES) m/z 336 (M+H⁺), 358 (M+Na⁺). Anal.calcd for C₁₄H₁₄FN₅O₂S: C, 50.14; H, 4.21; N, 20.88. Found: C, 50.18; H,4.26; N, 20.94.

EXAMPLE 23(S)-N-[[3-[4-[1-[1,2,4]Triazolyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide(25)

A stirred mixture of 26 (0.26 g, 0.938 mmol), ethyl dithioacetate (0.12g, 0.998 mmol), sodium fluoride (0.040 g, 0.953 mmol) and absolute EtOH(10 mL), under nitrogen, was treated during 5 min with a solution of0.97 M KOH (1.03 mL) in EtOH and kept at ambient temperature for 2 h. Itwas then diluted with CH₂CL₂ (75 mL), washed with water, 1M KHSO₄, waterand brine and evaporated. The residue was flash chromatographed onsilica gel with 5% MeOH—CHCl₃ and the product was crystallized from MeOHto give 0.118 g, mp 164-165° C. (dec) and 0.026 g, mp 162-163° C. (dec)of 25.

EXAMPLE 24(S)-N-[[3-[1-(Hydroxyacetyl)-5-indolinyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide(28)

A stirred, ice cold solution of 52 (8.80 g, 0.0240 mol) in CH₂Cl₂ (25mL) was treated during 20 min with a solution of trifluoroacetic acid(25 mL) in CH₂Cl₂ (10 mL). The mixture was kept in the ice bath for 2 h15 rain and concentrated under reduced pressure. A solution of theresidue in CH₂Cl₂ was washed with saturated NaHCO₃ and dilute NaCl,dried (Na₂SO₄) and concentrated. The residue was used in the nextreaction without further purification. A sample of this material (53)had: ¹H NMR (300 MHz, CDCl₃) d 3.00 (t, 2H), 3.54 (t, 2H), 3.85 (broads, 1H), 5.17 (s, 2H), 6.59 (d, 1H), 6.66 (broad s, 1H), 6.91 (d, 1H),7.23 (s, 1H), 7.36 (m, 5H); MS m/z 269 (M+H⁺).

An ice cold, stirred mixture of 53 (crude product from the previousreaction), acetone (200 mL), saturated NaHCO₃ (200 mL) and water (30 mL)was treated, dropwise during 20 min, with a solution of benzyloxyacetylchloride (4.70 mL, 0.030 mol) in acetone (55 mL), warmed slowly toambient temperature and kept for 18 h. Additional benzyloxytacetylchloride (1.0 mL) in acetone 35 mL) was added dropwise and the mixturewas kept at ambient temperature for an additional 3 h and diluted withEtOAc and water. A solid was collected by filtration and dried to give4.00 g of crude product. The EtOAc solution was dried (Na₂SO₄) andconcentrated to give 5.36 g of additional crude product. Crystallizationof the product from EtOAc gave a total of 6.35 g of 54¹⁴, mp 157-159.5°C. The analytical sample had: mp 158-159.5° C.; ¹H NMR (300 MHz, CDCl₃)δ 3,16 (t,2H), 4.01(t,2H), 4.21 (s, 2H), 4.69 (s, 2H), 5.19 (s, 2H),6.67 (s, 1H), 6.97 (d, 1H), 7.36 (m, 10H), 7.50 (braod s, 1H), 8.15 (d,1H); MS(EI) m/z (relative intensity) 416 (M⁺, 9), 310 (8), 202 (10), 133(8), 92 (8), 91 (99), 79 (7), 77 (9), 65 (12), 51 (6); IR (mull) 2381,1722, 1659, 1608, 1558 cm⁻¹. Anal. calcd for C₂₅H₂₄N₂O₄: C, 72.10; H,5.81; N, 6.73. Found: C, 72.05; H, 5.86; N, 6.68.

A stirred suspension of 54 (1.16 g, 2.78 mmol) in THF (42 mL) wascooled, under nitrogen, to −78° C. and treated, dropwise, during 5 rninwith 1.6 M n-BuLi in hexane (1.83 mL). It was kept at −78° C. for 50min, treated, dropwise, during 5 min with a solution of (R)-(−)-glycidylbutyrate (0.500 g, 3.47 mmol) in THF (2 mL), allowed to warm to ambienttemperature during 3 h and kpet for 18 h. It was then diluted withEtOAc, washed with saturated NH₄Cl, water and brine, dried (MgSO₄) andconcentrated. Chromatography of the residue on silica gel with 3%MeOH-0.2% NH₄OH—CHCl₃ gave 0.60 g (56%) of 55¹⁴: ¹H NMR [300 MHz,(CD₃)₂SO] δ 3.14 (t, 2H), 3.59 (m, 2H), 3.79 (d,d, 1H), 4.03 (m, 3H),4.29 (s, 2H), 4.58 (s, 2H), 4.65 (m, 1H), 5.20 (t, 1H), 7.31 (m, 6H),7.55 (s, 1H), 8.03 (d, 1H); MS(ES) m/z 383 (M+H⁺), 405 (M+Na⁺).

An ice cold, stirred mixture of 55 (0.60 g, 1.57 mmol), triethylamine(2.2 mL), and CH₂Cl₂ (12 mL), under nitrogen, was treated with3-nitrobenzenesulfonyl chloride (0.44 g, 1.99 mmol) and kept in the icebath for 30 min and at ambient temperature for 60 min. It was thendiluted with CH₂Cl₂, washed with water and brine, dried (Na₂SO₄) andconcentrated. Chromatography of the residue on silica gel with 15%CH₃CN—CH₂Cl₂ gave 0.70 g of 56: ¹H NMR (300 MHz, CDCl₃) d 3.19 (t, J=8.3Hz, 2H), 3.88 (d,d, 1H), 4.04 (t, J=8.4 Hz, 2H), 4.14 (t, 1H), 4.23 (s,2H), 4.42 (m, 2H), 4.70 (s, 2H), 4.84 (m, 1H), 6.97 (m, 1H), 7.34 (m,5H), 7.58 (s, 1H), 7.81 (t, 1H), 8.22 (m, 2H), 8.53 (m, 1H), 8.73 (m,1H); MS(ES) m/z 568 (M+H⁺), 590 (M+Na⁺).

A stirred mixture of 56 (crude product from 0.00314 mol of 55),acetonitride (70 mL), isopropanol (70 mL) and 29% ammonium hydroxide (70mL) was warmed at 40-44° C. for 7 h and kept at ambient temperature for18 h. It was concentrated in vacuo to an aqueous residue with wasextracted with CH₂Cl₂. The extract was washed with water and brine,dried (Na₂SO₄) and concentrated. Chromatography of the residue on silicagel with 8% MeOH-0.5% NH₄OH—CHCl₃ gave 1.05 g of 57: ¹H NMR [300 MHz,(CD₃)₂SO] d 2.78 (m, 2H), 3.13 (t, 2H), 3.82 (d,d, 1H), 4.01 (m, 3H),4.29 (s, 2H), 4.58 (s, 2H), 4.58 (m, 1H), 7.31 (m, 6H), 7.54 (broad s,1H), 8.03 (d, 1H); MS(ES) m/z 382 (M+H⁺), 404 (M+Na⁺).

A mixture of 57 (0.46 g, 1.21 mmol), MeOH (150 mL), 1 M HCl (1.2 mL) and5% palladium-on-carbon catalyst (250 mg) was hydrogenated at an initialpressure of 49 psi for 5 h. Additional 1M HCl (0.5 mL) and catalyst (100mg) were added and hydrogenation was continued for 18 h. The catalystwas removed by filtration and the filtrate was concentrated to give 0.34g of 27: ¹H NMR [300 MHz, (CD₃)₂SO] δ 3.15 (t, 2H), 3.22 (broad s, 2H),3.84 (d,d, 1H), 4.00 (t, 2H), 4.15 (s, 2H), 4.15 (m, 1H), 4.92 (m, 1H),7.24 (q, 1H), 7.50 (d, 1H), 8.03 (d, 1H), 8.37 (broad s, 3H); MS(ES) m/z2.92 (M+H⁺).

A suspension of 27 (0.10 g, 0.34 mmol) in a mixture of EtOH (15 mL) and0.97 M KOH (0.7 mL) was added, under nitrogen to a stirred mixture ofethyl dithioacetate (0.0412 g, 0.343 mmol) and sodium fluoride (0.0137g, 0.326 mmol) in EtOH (5 mL) and the mixture was kept at ambienttemperature for 2 h 15 min. Additional 0.97 M KOH (0.2 mL), sodiumiodide (6 mg) and ethyl dithioacetate (20 mg) were added and the mixturewas stirred for 2 h, mixed with CH₂Cl₂ (150 mL), washed with water, 1MKHSO4 and brine, dried (Na₂SO₄) and concentrated. The residue wascrystallized from acetone to give 0.0404 g of 28: mp 175-176° C. (dec);MS (FAB) m/z 350 (M+H⁺), 349 (M⁺), 331, 316, 205, 73; HR MS (FAB) calcdfor C₁₆H₂₀N₃O₄S (M+H⁺) 350.1174, found 350.1183; ¹H NMR [300 MHz,(CD₃)₂SO] d 2.42 (s, 3H), 3.14 (t, 2H), 3.79 (d,d, 1H), 3.89 (t, 2H),4.00 (t, 2H), 4.12 (m, 3H), 4.83 (t, 1H), 4.90 (m, 1H), 7.25 (d, 1H),7.50 (s, 1H), 8.03 (d, 1H), 10.35 (s, 1H); IR (DRIFT) 3255, 3223, 3068,1747, 1639, 1614 cm⁻¹.

EXAMPLE 25(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide(30)

A mixture of 58 (3.00 g, 7.00 mmol), THF (60 mL), absolute EtOH (100 mL)and 10% palladium-on-carbon catalyst (415 mg) was hydrogenated at aninitial pressure of 58 psi for 2 h 50 min. The catalyst was removed byfiltration and the filtrate was concentrated in vacuo to give 2.67 g of59 which was used without further purification in the next reaction: ¹HNMR (300 MHz, CDCl₃) d 2.16 (broad s), 3.02 (m, 8H), 3.73 (d,d, J=3.9,12.6 Hz, 1H), 3.96 (m, 3H), 4.72 (m, 1H), 6.92 (t, J=9.2 Hz, 1H), 7.11(m, 1H), 7.43 (d,d, J=2.6, 14.3 Hz, 1H); MS(ES) m/z 296 (M+H⁺).

A stirred, ice cold mixture of 59 (2.67 g from the previous reaction),acetone (190 mL) and saturated NaHCO₃ (70 mL) was treated, dropwiseduring 2-3 min with a solution of benzyloxyacetyl chloride (1.34 mL,8.61 mmol) in acetone (25 mL), kept in the ice bath for 1 h and dilutedwith EtOAc. The aqueous layer was extracted with EtOAc and the combinedorganic solution was washed with dilute NaCl, dried and concentrated.Chromatography of the residue on silica gel with 30% acetone-CH₂Cl₂ gave2.64 g of 60: ¹H NMR (300 MHz, CDCl₃) d 2.28 (broad s, 1H), 3.00 (m,4H), 3.66 (m, 2H), 3.77 (m, 3H), 3.96 (m, 3H), 4.22 (s, 2H), 4.61 (s,2H), 4.74 (m, 1H), 6.88 (t, J=9.2 Hz, 1H), 7.12 (m, 1H), 7.35 (s, 5H),7.46 (d,d, J=2.6, 14.2 Hz, 1H); IR (mull) 3406, 1748, 1647 cm⁻; HRMS(EI)calcd for C₂₃H₂₆FN₃O₅ (M⁺) 443.1856, found 443.1842.

A stirred, ice cold mixture of 60 (2.64 g, 6.00 mmol) and triethylamine(1.14 mL, 8.16 mmol) in CH₂Cl₂ (200 mL), under nitrogen, was treatedwith 3-nitrobenzenesulfonyl chloride (1.78 g, 8.04 mmol), warmed toambient temperature and kept for 5 h 20 min. Additional3-nitrobenzenesulfonyl chlroide (180 mg) and triethylamine (0.20 mL)were added and the mixture was kept at ambient temperature for 18 h,diluted with CH₂Cl₂ and washed with water and dilute NaCl, dried(Na₂SO₄) and concentrated. Chromatography of the residue on silica gelwith 40-60% acetone-hexane gave 3.36 g of 77: ¹H NMR (300 MHz, CDCl₃) d3.02 (broad s, 4H), 3.66 (broad s, 2H), 3.78 (broad s, 2H), 3.87 (d,d,J=5.9, 9.1 Hz, 1H), 4.09 (t, J=9.2 Hz, 1H), 4.22 (s, 2H), 4.41 (m, 2H),4.61 (s, 2H), 4.84 (m, 1H), 6.88 (t, J=9.1 Hz, 1H), 7.02 (m, 1H), 7.35(m, 6H), 7.82 (t, J=8.0 Hz, 1H), 8.23 (m, 1H), 8.53 (m, 1H), 8.73 (m,1H); MS(ES) m/z 629 (M+H⁺).

A solution of 77 (3.36 g, 5.34 mmol) in a mixture of acetonitrile (90mL), isopropanol (90 mL) and concentrated ammonium hydroxide (90 mL) waswarmed at 40-45° C. for 18 h, treated with additional ammonium hydroxide(30 mL), warmed at 40-45° C. for 8 h, treated with additional ammoniumhydroxide (25 mL) and warmed at 45° C. for 18 h. It was then mixed withwater and extracted with CH₂Cl₂. The extract was washed with diluteNaCl, dried (Na₂SO₄) and concentrated. Chromatography of the residue onsilica gel with 5% MeOH-0.5% NH₄OH—CHCl₃ gave 2.44 g of 61: ¹H NMR (300MHz, CDCl₃) d 1.50 (broad s), 3.04 (m, 6H), 3.65 (broad s, 2H), 3.81 (m,3H), 3.99 (t, 1H), 4.21 (s, 2H), 4.61 (s, 2H), 4.66 (m, 1H), 6.88 (t,1H), 7.12 (m, 1H), 7.33 (m, 5H), 7.47 (d,d, 1H); MS(ES) m/z 443 (M+H⁺).

A solution of 61 (1.45 g, 3.3 mmol) and 1.0 N HCl (3.65 mL) in 95% EtOH(150 mL) was treated with 5% palladium-on-carbon catalyst (500 mg) andhydrogenated at an initial pressure of 54 psi for 20 h 15 min.Additional 1.0 N HCl (0.5 mL) and catalyst (100 mg) were added andhydrogenation was continued for 20 h 30 min at an initial pressure of 60psi. The reaction was compete by TLC; it was neutralized withconcentrated NH₄OH, filtered and concentrated in vacuo to give 1.18 g of29: ¹H NMR [300 MHz, (CD₃)₂SO] d 2.94 (broad s, 4H), 3.19 (m, 2H), 3.48(broad s, 2H), 3.60 (broad s, 2H), 3.84 (m, 1H), 4.14 (m, 3H), 4.66(broad s, 1H), 4.93 (m, 1H), 7.07 (t, 1H), 7.16 (d,d, 1H), 7.48 (d,d,1H), 8.04 (broad s); IR (mull) 3420, 3099, 3040, 3008, 1755, 1641 cm⁻¹;MS(ES) m/z 353 (M+H⁺). Anal. calcd for C₁₆H₂₂ClFN₄O₄: C, 49.42; H, 5.70;Cl, 9.12; N, 14.41. Found: C, 48.16; H, 5.82; Cl, 10.00; N, 14.28.

A stirred mixture of ethyl dithioacetate (180 mL, 1.56 mmol), sodiumfluoride (72 mg, 1.7 mmol), 29 (500 mg, 1.29 mmol) and EtOH (70 mL)under nitrogen, was treated with 0.97M KOH (1.46 mL, 1.42 mmol) and theresulting solution was kept at ambient temperature for 3 h 35 min,diluted with CHCl₃, washed with water and dilute NaCl, dried (Na₂SO₄)and concentrated. Chromatography of the residue on silica gel with 5%MeOH-0.5% NH₄OH—CHCl₃ and crystallization of the resulting product fromabsolute EtOH gave 0.238 mg (44.9%) 30: mp 163-165° C.; ¹H NMR (300 MHz,CDCl₃) d 2.60 (s, 3H), 3.06 (m, 4H), 3.45 (m, 2H), 3.61 (m, 1H), 3.82(m, 3H), 4.07 (m, 2H), 4.25 (m, 3H), 4.97 (m, 1H), 6.91 (t, 1H), 7.07(m, 1H), 7.45 (d.d, 1H), 7.91 (broad s, 1H); MS(FAB) m/z (relativeintensity) 411 (M+H⁺, 100), 410 (M⁺, 66.5), 266 (3.1); IR 3292, 1733,1653 cm⁻¹. Anal. calcd for C₁₈H₂₃FN₄O₄S: C, 52.67; H, 5.65; N, 13.65.Found: C, 52.76; H, 5.58; N, 13.64.

EXAMPLE 26(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thio-acetamide(32)

An ice cold, stirred mixture of 31 (0.38 g, 0.0012 mol) andtriethylamine (0.38 mL, 0.0027 mol) in THF (12 mL), under nitrogen, wastreated with ethyl dithioacetate (0.16 mL, 0.0014 mol) and then kept atambient temperature for 24.5 h and concentrated in vacuo. A solution ofthe residue in CH₂Cl₂ was washed with saturated NaHCO₃, water and brine,dried (MgSO₄) and concentrated. Crystallization of the residue fromEtOAc-hexane gave 0.355 g of 32: mp 155-156° C.; MS(ES) m/z 370 (M+H⁺),392 (M+Na⁺); IR (DRIFT) 3206, 3042, 1759, 1738 cm⁻¹; ¹H NMR (300 MHz,CDCl₃) d 2.60 (s, 3H), 2.95 (s, 4H), 3.43 (m, 4H), 3.82 (d, d, 1H), 4.08(m, 2H), 4.27 (m, 1H), 4.98 (m, 1H), 7.06 (m, 1H), 7.33 (broad s, 1H),7.51 (d, 1H), 8.03 (broad s, 1H). Anal. calcd for C₁₆H₂₀FN₃O₂S₂: C,52.01; H, 5.46; N, 11.37. Found: C, 51.86; H, 5.43; N, 11.20.

EXAMPLE 27(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thio-acetamide,thiomorpholine S-oxide (34)

An ice cold, stirred mixture of sodium metaperiodate (1.08 g, 5.05 mmol)and water (12 mL), under nitrogen, was treated with 62 (1.5 g, 4.8 mmol)and MeOH (17 mL) and kept at 6° C. for 18 h and at 4° C. for 3 h. It wasthen treated with additional sodium metaperiodate (0.1 g), kept at 4° C.for 3 h and extracted with CHCl₃. The extract was dried (MgSO₄) andconcntrated to give 1.4 g of 63: ¹H NMR [300 MHz, (CD₃)₂SO] d 2.84 (m,2H), 3.01 (m, 2H), 3.16 (m, 2H), 3.50 (m, 3H), 3.65 (m, 1H), 3.77 (d,d,1H), 4.03 (t, 1H), 4.66 (m, 1H), 5.18 (t, 1H), 7.16 (m, 2H), 7.52 (m,1H); MS(ES) m/z 329 (M+H⁺), 351 (M+Na⁺).

An ice cold, stirred mixture of 63 (1.27 g, 3.87 mmol) and triethylamine(0.732 mL, 5.25 mmol) in CH₂Cl₂ (130 mL), under nitrogen, was treatedwith m-nitrobenzenesulfonyl chloride (1.15 g, 5.19 mmol) and kept atambient temperature for about 24 h. It was diluted with CH₂Cl₂, washedwith water and brine, dried (Na₂SO₄) and concentrated to give 78 whichwas used in the next reaction without purification.

A stirred mixture of the product (78) from the previous reaction,acetonitrile (70 mL) and isopropanol (70 mL) was treated withconcentrated ammonium hydroxide (70 mL, 29.9% NH₃) and kept at 40° C.for 2 h, at ambient temperature for 18 h and at 40-45° C. for 4 h; itwas concentrated to about 50 mL, diluted with water and extracted withCH₂Cl₂. The extracts were washed with water and brine, dried (MgSO₄) andconcentrated. Chromatography of the residue on silica gel with 5%MeOH—CHCl₃ gave 0.58 g of 33: MS(ES) m/z 328 (M+H⁺), 350 (M+Na⁺); ¹H NMR[300 MHz, (CD₃)₂SO] d 2.81 (m, 4H), 3.01 (m, 2H), 3.16 (m, 2H), 3.30(broad s), 3.49 (m, 2H), 3.80 (d,d, 1H), 4.01 (t, 1H), 4.58 (m, 1H),7.19 (m, 2H), 7.51 (m, 1H).

A stirred suspension of 33 (3.7 g, 0.011 mol) and triethylamine (3.5 mL,0.025 mol) in THF (120 mL) was cooled, in an ice bath, under nitrogen,treated, dropwise during 2 min, with a solution of ethyl dithioacetate(1.47 mL, 0.0128 mol) in THF (2 mL) and kept at ambient temperature for22 h. The resulting solution was concentrated and the residuecrystallized from acetonitrile to give 3.61 g of 34: mp 176-177° C.; ¹HNMR [300 MHz, (CD₃)₂SO] d 2.42 (s, 3H), 2.85 (m, 2H), 3.01 (m, 2H), 3.18(m, 3H), 3.50 (m, 2H), 3.78 (d,d, 1H), 3.89 (broad s, 2H), 4.12 (t, 1H),4.92 (m, 1H), 7.18 (m, 2H), 7.49 (m, 1H), 10.33 (s, 1H); IR (DRIFT)3186, 3102, 1741 cm⁻¹; MS(ES) m/z 386 (M+H⁺), 408 (M+Na⁺). Anal. calcdfor C₁₆H₂₀FN₃O₃S₂.0.5 H₂O: C, 48.71; H, 5.37; N, 10.65; S, 16.26; H₂O,2.38. Found: C, 48.75; H, 5.17; N, 10.72; S, 16.07; H₂O, 1.72.

EXAMPLE 28(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thio-acetamide,thiomorpholine S, S-dioxide (36)

A stirred mixture of 62 (0.399 g, 0.00128 mol) in 25% water/acetone (12mL), under nitrogen was treated with N-methylmorpholine, N-oxide (0.45g, 0.00384 mol) and 0.1 mL of a 2.5 wt % solution of osmium tetroxide intert-butanol. It was kept at ambient temperature for 18 h, mixed withsaturated NaHSO₃ (50 mL) and extracted with CH₂Cl₂. The extract waswashed with saturated NaHSO₃ and brine, dried (Na₂SO₄) and concentrated.The residue was mixed with 3.5% MeOH—CH₂Cl₂ and filtered; the solid wasdissolved in 15% MeOH—CH₂Cl₂ and concentrated to give 0.29 g of 64. Thefiltrate was chromatographed on silica gel with 3.5% MeOH—CH₂Cl₂ to give0.1 of additional 64: MS(ES) m/z 345 (M+H⁺), 367 (M+Na⁺); ¹H NMR [300MHz, (CD₃)₂SO] d 3.26 (m, 4H), 3.44 (m, 4H), 3.60 (m, 2H), 3.80 (d,d,1H), 4.05 (t, 1H), 4.69 (m, 1H), 7.22 (m, 2H), 7.54 (d, 1H).

A stirred mixture of 64 (0.39 g, 0.00113 mol) and triethylamine (0.214mL, 0.00154 mol) in CH₂Cl₂ (37 mL) was cooled, under nitrogen, in an icebath and treated, portionwise during 5 min, with 3-nitrobenzenesulfonylchloride (0.335 g, 0.00151 mol). The mixture was kept in the ice bathfor 20 min and at ambient temperature for 18 h and concentrated invacuo. A stirred solution of the residue in 2-propanol (25 mL) andacetonitrile (25 mL), under nitrogen, was treated with 30% NH₄OH (25mL), warmed at 50-55° C. for 6 h and kept at ambient temperature for 48h. It was concentrated to remove the organic solvents, diluted withwater and extracted with CH₂Cl₂. The extract was washed with water andbrine, dried (MgSO₄) and concentrated. Flash chromatography of theresidue on silica gel with 6% MeOH-0.4% NH₄OH—CHCl₃ gave 0.29 g of 35:¹H NMR [300 MHz, (CD₃)₂SO] d 1.59 (broad s, 2H), 2.78 (m, 2H), 3.24 (m,4H), 3.43 (m, 4H), 3.81 (d,d, 1H), 4.01 (t, 1H), 4.57 (m, 1H), 7.18 (m,2H), 7.52 (m, 1H); MS(ES) m/z 344 (M+H⁺), 366 (M+Na⁺).

A stirred, ice cold suspension of 35 (0.28 g, 0.85 mmol) in a mixture ofEt₃N (0.26 mL, 1.9 mmmol) and THF (10 naL) was treated with ethyldithioacetate (0.11 mL, about 6 drops) and kept in the ice bath for 20min and then at ambient temperature; the reaction was followed by TLC.After 20 h there was still a suspension and only partial reaction;additional THF (10 mL) and ethyl dithioacetate (3 drops) were added.After an additional 48 h the reaction was still incomplete; thesuspension was treated with CH₂Cl₂ (10 mL) and kept for 72 h. At thistime almost complete solution and an almost complete conversion toproduct had been obtained. An additional drop of ethyl dithioacetate wasadded and the mixture was kept at ambient temperature for 5 d andconcentrated in vacuo. The residue was mixed with EtOAc, washed withsaturated NaHCO₃, water and brine, dried (MgSO₄) and concentrated.Crystallization of the residue from MeOH—EtOAc gave 0.209 g of 36: mp197-198° C.; ¹H NMR [300 MHz, (CD₃)₂SO] d 2.42 (s, 3H), 3.24 (m, 4H),3.43 (m, 4H), 3.78 (d,d, 1H), 3.88 (m, 2H), 4.12 (t, 1H), 4.92 (m, 1H),7.18 (m, 2H), 7.50 (m, 1H), 10.37 (broad s, 1H); IR (mull) 3300, 3267,1743 cm⁻¹; MS(ES) m/z 424 (M+Na⁺). Anal. calcd for C₁₆H₂₀FN₃O₄S₂: C,47.87; H, 5.02; N, 10.47. Found: C, 47.84; H, 5.23; N, 10.28.

EXAMPLE 29(S)-N-[[3-[3,5-Difluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide(38)

A stirred mixture of 65 (1.8 g, 0.00396 mol), pyridine (30 mL) andabsolute EtOH (3 mL), under nitrogen, was treated with hydroxylaminehydrochloride (1.44 g, 0.0207 mol), warmed to the reflux temperatureduring 2 h, refluxed for 3.5 h, kept at ambient temperature for 18 h andat reflux for 4 h. It was concentrated in vacuo and the residue wasmixed with water, adjusted to pH 11 with saturated NaHCO₃ and extractedwith Et₂O. The extracts were washed with brine, dried (Na₂SO₄) andconcentrated. Chromatography of the residue on silica gel with 5%MeOH-0.35% NH₄OH—CHCl₃ gave 0.75 g of recovered 65 and 0.72 g of 66: ¹HNMR [300 MHz, (CD₃)₂SO] d 1.40 (s, 9H), 1.72 (broad s, 2H), 2.78 (m,2H), 2.97 (m, 4H), 3,40 (m, 4H), 3.80 (d,d, 1H), 4.00 (t, 1H), 4.59 (m,1H), 7.27 (d, 2H); MS(ES) m/z 413 (M+H⁺), 435 (M+Na⁺).

An ice cold, stirred mixture of 66 (0.75 g, 0.0018 mol) andtriethylamine (0.315 mL, 0.00225 mol) in THF (12 mL), under nitrogen,was treated, dropwise with benzyl chloroformate (0.29 mL, 0.0020 mol),kept in the ice bath for 15 min and at ambient temperature for 2 h andconcentrated in vacuo. The residue was mixed with CH₂Cl₂ and washed withsaturated NaHCO₃, water and brine, dried (Na₂SO₄) and concentrated. Thisresidue was mixed with Et₂O and filtered to give 0.939 g of 67: mp116-118° C.; ¹H NMR (300 MHz, CDCl₃) d 1.48 (s, 9H), 3.08 (m, 4H), 3.53(m, 4H), 3.60 (m, 2H), 3.73 (m, 1H), 3.96 (t, 1H), 4.76 (m, 1H), 5.10(s, 2H), 5.21 (m, 1H), 7.07 (d, 2H), 7.31 (s, 5H); MS(ES) m/z 547(M+H⁺), 569 (M+Na⁺).

Compound 67 (0.805 g, 0.00147 mol) was added with stirring, portionwiseduring 5 min, under nitrogen, to ice cold trifluoroacetic acid (9 mL).The resulting solution was kept in the ice bath for 1 h and thenconcentrated under a stream of nitrogen. The residue was mixed with iceand saturated NaHCO₃ and extracted with CH₂Cl₂; the extract was washedwith water and brine, dried (Na₂SO₄) and concentrated to give 0.63 g ofproduct. The combined aqueous layer was reextracted with EtOAc; theextracts were washed with water and brine, dried (Na₂SO₄) andconcntrated to give additional product. The combined product amounted to0.68 g of 68 which was used in the next reaction without furtherpurification.

An ice cold, stirred mixture of 68 (0.68 g, 0.00152 mol), saturatedNaHCO₃ (15.2 mL) and acetone (40 mL), under nitrogen was treated,dropwise during 15 min, with a solution of benzyloxyacetyl chloride(0.29 mL, 0.0019 mol) in acetone (5 mL), kept at ambient temperature for6 h, diluted with EtOAc and washed with water and brine. The extract wasdried (MgSO₄) and concentrated in vacuo to give 0.72 g of 69: MS(ES) m/z395 (M+H⁺), 617 (M+Na⁺); ¹H NMR (300 MHz, CDCl₃) d 3.12 (m, 4H), 3.59(m, 4H), 3.74 (m, 3H), 3.96 (t, 1H), 4.22 (s, 2H), 4.62 (s, 2H), 4.75(broad s, 1H), 5.10 (s, 2H), 5.22 (m, 1H), 7.08 (d, 2H), 7.33 (m, 10H).

A mixture of 69 (0.72 g, 0.0012 mol), MeOH and 5% palladium-on-carboncatalyst (0.4 g) was hydrogenated at an initial pressure of 45 psi for 4h. By TLC (8% MeOH-0.5% NH₄OH—CHCl₃) the starting material had beenreduced and two products formed. 1M Hydrochloric acid (1.34 mL) wasadded and hydrogenation was continued at an initial pressure of 40 psifor 21 h. By TLC only the more polar product remained. The catalyst wasremoved by filtration and the filtrate was concentrated to give 0.40 gof 37: MS(ES) m/z 371 (M+H⁺), 393 (M+Na⁺); ¹H NMR [300 MHz, (CD₃)₂SO] d3.02 (s, 4H), 3.20 (m, 2H), 3.43 (s, 2H), 3.56 (s, 2H), 3.84 (m, 1H),3.84 (broad s), 4.10 (s, 2H), 4.14 (t, 1H), 4.96 (m, 1H), 7.26 (d, 2H),8.41 (broad s, 3H).

A stirred suspension of 37 (0.38 g) in a solution of Et₃N (0.31 mL) andTHF (10 mL), under nitrogen, was treated with ethyl dithioacetate (0.13mL, about 7 drops) and kept at ambient temperature for 7 d; the reactionwas followed by TLC (8% MeOH-0.5% NH₄OH—CHCl₃). Additional ethyldithioacetate (2 drops) was added after 24 h; after 30 h CH₂Cl₂ (10 mL)and ethyl dithioacetate (3 drops) were added; after 48 h additionaltriethylamine (0.3 mL) was added. The mixture was concentrated in vacuoand the residue was mixed with ice and saturated NaHCO₃ an extractedwith CH₂Cl₂. The extract was washed with water and brine, dried (MgSO₄)and concentrated. The residue was chromatographed on silica gel with2.5% MeOH—CH₂Cl₂ and the product was crystallized from MeOH to give0.182 g of 38: mp 110-111° C. (dec); MS(ES) m/z 429 (M+H⁺), 451 (M+Na⁺);HRMS (FAB) caled for C₁₈H₂₃F₂N₄O₄S (M+H⁺) 429.1408, found 429.1415; IR(DRIFT) 1760, 1652, 1639 cm⁻¹; [α²⁴ _(D)8° (MeOH).

EXAMPLE 30(S)-N-[[3-[4-[1-[1,2,4]Triazolyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea(44)

A solution of 26 (0.190 g, 0.685 mmol) in CH₂Cl₂ (20 mL) was added,dropwise during 20 min, under nitrogen, to an ice cold, stirred solutionof 1,1¢-thiocarbonyldi-2(1H)-pyridone (0.193 g, 0.831 mmol) in CH₂Cl₂ (7mL). The mixture was kept in the ice bath for 20 min and at ambienttemperature for 2 h, diluted with CH₂Cl₂, washed with water and brine,dried (MgSO₄) and concentrated. Chromatography of the residue on silicagel with 10-15% CH₃CN—CH₂Cl₂ gave 0.11 g of 79 which was used in thenext reaction without further purification: MS(ES) m/z 320 (M+H⁺), 342(M+Na⁺).

A stirred, ice cold solution of 79 (0.10 g, 0.31 mmol) in THF (15 mL)was treated with excess anhydrous ammonia and kept in the ice bath for90 min. It was then evaporated under a stream of nitrogen to a volume ofabout 5 mL to give a solid which was collected by filtration and washedwith cold THF to give 0.105 g of 44: mp 214-215° C.; ¹H NMR [300 MHz,(CD₃)₂SO] d 3.82 (m, 3H), 4.18 (t, 1H), 4.89 (broad s, 1H), 7.20 (broads, 2H), 7.50 (d, 1H), 7.79 (m, 2H), 7.93 (t, 1H), 8.26 (s, 1H), 8.97 (s,1H); MS(ES) m/z 337 (M+H⁺), 359 (M+Na⁺). Anal. calcd for C₁₃H₁₃FN₆O₂S:C, 46.42; H, 3.90; N, 24.99. Found: C, 46.22; H, 3.98; N, 24.55.

EXAMPLE 31(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2oxo-5-oxazolidinyl]-methyl]thiourea(45)

An ice cold, stirred solution of 1,1¢-thiocarbonyl-2(1H)-dipyridone(0.123 g, 0.530 mmol) in CH₂Cl₂ (5 mL), under nitrogen, was treated witha suspension of 29 (0.17 g, 0.4 mmol) in CH₂Cl₂ (20 mL) and then during10 min with a solution of triethylamine (0.111 mL, 0.8 nmmol) in CH₂Cl₂(10 mL). It was kept in the ice bath for 30 min, at ambient temperaturefor 2 h and at <0° C. for 18 h. It was then diluted with CH₂Cl₂, washedwith water and brine, dried (MgSO₄) and concentrated. The residue (80)was used without further purification in the next reaction. A sample of80 that was purified by flash chromatography on silica gel with 10-20%acetonitrile-CH₂Cl₂ had: ¹H NMR (300 MHz, CDCl₃) d 1.60 (broad s), 3.07(m, 4H), 3.45 (m, 2H), 3.85 (m, 4H), 3.97 (d,d, 1H), 4.16 (t, 1H), 4.21(s, 2H), 4.82 (m, 1H), 6.95 (t, 1H), 7.13 (d,d, 1H), 7.47 (d,d, 1H); MSm/z 395 (M+H⁺); 417 (M+Na⁺).

Excess anhydrous ammonia was bubbled into a stirred, ice cold solutionof 80 (crude product from the previous reaction) in THF (25 mL) and themixture was kept in the ice bath for 90 min and concentrated under astream of nitrogen. The residue was chromatographed on silica gel with5% MeOH-0.4% NH₄OH—CHCl₃ and the product was crystallized fromacetonitrile to give 0.0544 g of 45: mp 209-210° C.; ¹H NMR [300 MHz,(CD₃)₂SO] d 294 (broad s, 4H), 3.47 (broad s, 2H), 3.60 (broad s, 2H),3.78 (broad s, 3H), 4.07 (t, 1H), 4.10 (d, J=5.5 Hz, 2H), 4.63 (t, J=5.5Hz, 1H), 4.81 (broad s, 1H), 7.05 (t, 1H), 7.16 (d,d, 1H), 7.15 (broads, 2H), 7.49 (d,d, 1H), 7.91 (t, 1H); IR (mull) 3443, 3403, 3321, 3202,3081, 1753, 1655, 1648 cm⁻¹; HRMS (FAB) calcd for C₁₇H₂₃FN₄O₄S (M+H⁺)412.1454, found 412.1447. Anal. calcd for C₁₇H₂₂FN₅O₄S: C, 49.63; H,5.39; N, 17.02. Found: C, 49.63; H, 5.48; N, 16.99.

EXAMPLE 32 (S)-N-[[3-[1-(Hydroxyacetyl)-5-indolinyl]-2-oxo-5-5oxazolidinyl]methyl]thiourea (46)

An ice cold, stirred solution of 1,1¢-thiocarbonyldi-2(1H)-pyridone(0.096 g, 0.41 mmol) in CH₂Cl₂ (5 mL) was treated with a suspension of27 (0.10 g, 0.34 mmol) in CH₂Cl₂ (15 mL) and then with 0.05 mL (0.36mmol) of triethylamine. It was kept in the ice bath for 30 min and atambient temperature for 2 h, diluted with CH₂Cl₂, washed with water andbrine, dried (MgSO₄) and concentrated. Chromatography of the residue onsilica gel with 20-40% CH₃CN—CH₂Cl₂ gave 0.04 g of 81.

Excess anhydrous ammonia was bubbled into an ice cold solution of 81(0.04 g) in THF (30 mL) and the mixture was kept in the ice bath for 80min and concentrated under a stream of nitrogen. The residue wascrystallized from CH₃CN to give 0.0151 g of 46: mp 214-215° C. (dec); MS(FAB) m/z 351 (M+H⁺), 350 (M⁺), 319, 304, 147; HRMS (FAB) calcd forC₁₅H₁₉N₄O₄S (M+H⁺) 351.1127, found 351.1130; IR (DRIFT) 3329, 3296,3196, 1746, 1655, 1626 cm⁻¹.

EXAMPLE 33(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea,thiomorpholine S-oxide (47)

A suspension of 33 (0.30 g, 0.92 mmol) in CH₂Cl₂ (7 mL) was added,during 20 min, to an ice cold, stirred mixture of1,1¢-thiocarbonyldi-2(1H)-pyridone (0.258 g, 1.11 mmol) and CH₂Cl₂ (20mL). The mixture was kept in the ice bath for 20 min and at ambienttemperature for 2 h, mixed with CH₂Cl₂ (50 mL), washed with water andbrine, dried (MgSO₄) and concentrated. Chromatography of the product onsilica gel with 20-50% CH₃CN—CH₂Cl₂ gave 0.27 g of 82 which was used inthe next reaction: MS(ES) m/z 370 (M+H⁺), 392 (M+Na⁺).

A stirred, ice cold solution of 82 (0.27g , 0.73 mmol) in THF (15 mL),under nitrogen, was treated with excess anhydrous ammonia, kept in theice bath for 1 h and concentrated; crystallization of the residue fromMeOH gave 0.175 g of 47; mp 212-213° C.; ¹H NMR [300 MHz, (CD₃)₂SO] d2.83 (m, 2H), 3.01 (m, 2H), 3.17 (m, 2H), 3.50 (t, 2H), 3.78 (broad s,3H), 4.08 (t, 1H), 4.80 (broad s, 1H), 7.17 (m, 2H), 7.17 (broad s, 2H),7.50 (d, 1H), 7.90 (t, 1H); MS(ES) m/z 409 (M+Na⁺); IR (mull) 3335,3284, 3211, 3175, 3097, 1750, 1630 cm⁻¹. Anal. calcd for C₁₅H₁₉FN₄O₃S₂:C, 46.62; H, 4.95; N, 14.50. Found: C, 46.50; H, 4.95; N, 14.40.

EXAMPLE 34(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl-S-methyldithiocarbamate(48)

An ice cold, stirred mixture of 39 (0.59 g, 0.0020 mol), EtOH (1.5 mL),water (2 drops) and triethylamine (0.613 mL, 0.00440 mol), undernitrogen, was treated with carbon disulfide (0.066 mL, 0.0011 mol) andkept in the ice bath for 2 h and at ambient temperature for 18 h. (Asolution was obtained after the addition of carbon disulfide; a whiteprecipitate began to form soon after the mixture was warmed to ambienttemperature.) The thick suspension was treated, dropwise during 2 min,with a solution of methyl iodide (0.137 mL, 0.00220 mol) in EtOH (2 mL)and the mixture was kept at ambient temperature for 1.5 h andconcentrated in vacuo. A solution of the residue in EtOAc was washedwith saturated NaHCO₃, water and brine, dried (MgSO₄) and concentrated.The residue was chromatographed on silica gel with 1.8% MeOH—CH₂Cl₂ andthe product was crystallized from EtOAc to give 0.197 g of 48: mp154-155° C.; IR (mull) 3354, 3346, 1726 cm⁻¹. Anal. calcd forC₁₆H₂₀FN₃O₃S₂: C, 49.85; H, 5.23; N, 10.90. Found: C, 49.73; H, 5.25; N,10.82.

EXAMPLE 35(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl-O-methylthiocarbamate(50)

A stirred mixture of 48 (0.200 g, 0.518 mmol), sodium methoxide (0.003g, 0.06 mmol) and MeOH (5 mL), under nitrogen, was refluxed for 4 h andkept at ambient temperature for 18 h. It was found that the startingmaterial and product had similar mobilities on TLC. the reaction wastherefore followed by MS(ES). Starting material was still present. Themixture was refluxed for 3 h, additional sodium methoxide (0.005 g) wasadded and reflux was continued for 2 h. It was kept at ambienttemperature for 18 h, refluxed for 1 h, kept at ambient temperature 1.5h and concentrated in vacuo. The residue was mixed with ice, the pH wasadjusted to 9-10 with 1M KHSO4 and saturated NaHCO₃ and the mixture wasextracted with CH₂Cl₂. The extract was washed with water and brine,dried (MgSO₄) and concentrated. The residue was chromatographed onsilica gel with 5% acetone-CH₂Cl₂ and the product was crystallized fromEtOAc-hexane to give 0.107 g of 50: mp 128-129° C.; MS(ES) m/z 370(M+H⁺), 392 (M+Na⁺); IR (DRIFT) 3282, 3251, 1753, 1735 cm⁻¹; ¹H NMR [300MHz, (CD₃)₂SO] d 2.94 (m, 4H), 3.47, 374 (m,m, 7H), 3.86, 3.91 (s,s,3H), 4.10 (m, 1H), 4.73, 4.86 (m,m, 1H), 7.05 (t, 1H), 7.16 (d,d, 1H),7.47 (d,d, 1H), 9.41, 9.50 (s,s, 1H). Anal. calcd for C₁₆H₂₀FN₃O₄S: C,52.02; H, 5.46; N, 11.38. Found: C, 51.97; H, 5.49; N, 11.35.

When in the procedure of Example 35 an appropriate amount of sodiumethoxide was substituted for sodium methoxide, the compound of Example36 below in Table A was obtained.

When in the procedure of Example 1 an appropriate amount of(S)-N-[[3-[3-fluoro-4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]isopropylcarboxamide,(S)-N-[[3-[3-fluoro-4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropylcarboxamide,or(S)-N-[[3-[3,5-difluoro-4-morpholinyl]phenyl]-2-oxo-5-oxazolidiny]methyl]acetamidewas substituted for(S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]-methyl]acetamide(Compound 11) and the general procedures of Example 1 was followed, thecompounds of Examples 37, 38 and 39 respectively as set forth below inTable A were obtained. The isopropylcarboxamide and thecyclopropylcarboxamide are obtained by following the procedure inExample 5 of U.S. Pat. No. 5,688,792 only substituting isobutyricanhydride and cyclopropane carbonyl chloride respectively for aceticanhydride in step 7. The acetamide is obtained as described in U.S. Pat.No. 5,688,792 at Example 4.

When in the procedure of Example 5, step B, an excess amount ofdimethylamine in THF is substituted for anhydrous ammonia, the compoundof Example 40 set forth below in Table A is obtained.

TABLE A

Example No. Compound R, R′ 36 (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)- R =H, R′ = OC₂H₅ phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthiocarbamate; mp 120° C., MS(ES) m/z 384 (M + H⁺). Anal. calcd forC₁₇H₂₂FN₃O₄S: C, 53.25; H, 5.78; N, 10.96. Found: C, 53.23; H, 5.82; N,10.92. 37 (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)- R = H, R′ = CH(CH₃)₂phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide; mp152-153° C. (dec.); Anal. calcd for C₁₈H₂₄FN₃O₃S: C, 56.67; H, 6.34; N,11.02. Found: C, 56.58; H, 6.41; N, 10.81 38(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)-phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropane-carbothioamide; mp155-156° C.; Anal. calcd for C₁₈H₂₂FN₃O₃S: C, 56.98; H, 5.84; N, 11.07.Found: C, 56.98; H, 5.85; N, 10.97

39 (S)-N-[[3-[3,5-Difluoro-4-(4-morpholinyl)- R = F, R′ = CH₃phenyl]-2-oxo-5-oxazolidinyl]methyl]- thioacetamide 40(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)- R = H, R′ = N(CH₃)₂phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′- dimethylthiourea PREPARATIONZ Methyl Dithiopropionate

A stirred mixture of magnesium turnings (12.6 g, 0.520 g atom) and THF(100 mL) under nitrogen is treated with a crystal of iodine and about 5%of a solution of bromoethane (30.0 mL, 0.40 mol) in THF (200 mL). Whenthe reaction starts, the remainder of the bromoethane solution is added,dropwise at a rate sufficient to maintain a gentle reflux. After theaddition, stirring is continued for 1 hour; the resulting solution iscooled to −20° C. and treated, during 10 minutes with carbon disulfide(24.0 mL, 0.40 mol). The mixture is warmed to 15° C., treated withmethyl iodide (28.0 mL, 0.45 mol) and kept at 60° C. for 1 hour. It isthen cooled in an ice bath, treated with ice and extracted with Et₂O.The extract is washed with brine, dried (MgSO₄) and concentrated.Distillation of the residue gives 34.0 g of the titled product, bp48-52° C. (12 mmHg).

The following methyl dithio compounds were obtained when the appropriatealkyl magnesium bromide was substituted for ethyl magnesium bromide inthe above procedure:

The following methyl dithio compounds were obtained when the appropriatealkyl magnesium bromide was substituted for ethyl magnesium bromide inthe above procedure:

TABLE B

Rs = (b) (CH₃)₂CH— (c)

(d) CH₃CH₂CH₂— (e)

(f)

(g) (CH₃)₃C—CH₂— (h)

(i)

(j)

(k)

(l)

(m)

When following the general procedure of Example 27, step 4, anappropriate amount of the amine listed below is reacted with the dithiocompound listed below the respective compounds, Examples 41 to 61 ofTable C are obtained.

When following the general procedure of Example 25, step 6, anappropriate amount of the amine listed below is reacted with the dithiocompound listed below, the respective compounds, Examples 62 to 67, ofTable C are obtained.

TABLE C Example Dithio Compound No. Compound Amine (from Preparation Z)41 (S)-N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide, thiomorpholine S-oxide; mp196-197° C.; Anal. calcd for C₁₇H₂₂FN₃O₃S₂: C, 51.11; H, 5.55; N, 10.52;S, 16.05. Found: C, 50.99; H, 5.60; N, 10.55; S, 15.75

Z (a) 42 S)-N-[[3-[3-Fluoro-4-(4- Same as above Z (b) thiomorpholinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide,thiomorpholine S-oxide; mp 195-196° C.; Anal. calcd for C₁₈H₂₄FN₃O₃S₂:C, 52.28; H, 5.85; N, 10.16; S, 15.51. Found: C, 52.24; H, 5.97; N,10.16; S, 15.28 43 (S)-N-[[3-[3-Fluoro-4- Same as above Z (c)(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-cyclopropanecarbothio- amide, thiomorpholine S-oxide; mp 109-110° C.;Anal. calcd for C₁₈H₂₂FN₃O₃S₂: C, 52.54; H, 5.39; N, 10.21; S, 15.58.Found: C, 52.48; H, 5.51; N, 10.28; S, 15.29 44 (S)-N-[[3-[3-Fluoro-4-Same as above Z (d) (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- butanethioamide, thiomorpholine S-oxide 45(S)-N-[[3-[3-Fluoro-4- Same as above Z (e) (4-thiomorpholinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]-3- methylbutanethioamide,thiomorpholine S-oxide 46 (S)-N-[[3-[3-Fluoro-4- Same as above Z (f)(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-methylbutanethioamide, thiomorpholine S-oxide 47 (S)-N-[[3-[3-Fluoro-4-Same as above Z (g) (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- 3,3-dimethylbutanethio- amide, thiomorpholineS-oxide 48 (S)-N-[[3-[3-Fluoro-4- Same as above Z (h)(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-cyclobutanecarbothio- amide, thiomorpholine S-oxide 49(S)-N-[[3-[3-Fluoro-4- Same as above Z (i) (4-thiomorpholinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- cyclopentanecarbothio- amide,thiomorpholine S-oxide 50 (S)-N-[[3-[3-Fluoro-4- Same as above Z (j)(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-cyclohexanecarbothio- amide, thiomorpholine S-oxide 51(S)-N-[[3-[3-Fluoro-4- Same as above Z (k) (4-thiomorpholinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopropylethanethio- amide,thiomorpholine S-oxide 52 (S)-N-[[3-[3-Fluoro-4- Same as above Z (l)(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-cyclobutylethanethio- amide, thiomorpholine S-oxide 53(S)-N-[[3-[3-Fluoro-4- Same as above Z (m) (4-thiomorpholinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopentylethanethio- amide,thiomorpholine S-oxide 54 (S)-N-[[3-[3,5-Difluoro-4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-thioacetamide, thiomorpholine S-oxide

Ethyl dithioacetate 55 (S)-N-[[3-[3,5-Difluoro- Same as above Z (a)4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-propanethioamide, thiomorpholine S-oxide 56 (S)-N-[[3-[3,5-Difluoro-Same as above Z (b) 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethio- amide, thiomorpholine S-oxide57 (S)-N-[[3-[3,5-Difluoro- Same as above Z (c) 4-(4-thiomorpholinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide,thiomorpholine S-oxide 58 (S)-N-[[3-[4-(4- thiomorpholinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]- thioacetamide, thiomorpholineS-oxide

Ethyl dithioacetate 59 (S)-N-[[3-[4-(4- Same as above Z (a)thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-propanethioamide, thiomorpholine S-oxide 60 (S)-N-[[3-[4-(4- Same asabove Z (b) thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-methylpropanethio- amide, thiomorpholine S-oxide 61 (S)-N-[[3-[4-(4-Same as above Z (c) thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothio- amide, thiomorpholineS-oxide 62 (S)-N-[[3-[3,5-Difluoro- 4-(4-hydroxyacetyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]- methyl]propanethio- amide

Z (a) 63 (S)-N-[[3-[3,5-Difluoro- Same as above Z (b)4-(4-hydroxyacetyl)-1- piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]-methyl]-2-methyl- propanethioamide 64 (S)-N-[[3-[3,5-Difluoro- Same asabove Z (c) 4-(4-hydroxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]cyclopropane- thioamide 65 (S)-N-[[3-[3-[4-(hydroxyacetyl)-1- piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]-methyl]propanethio- amide

Z (a) 66 (S)-N-[[3-[3-[4- Same as above Z (b) (hydroxyacetyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]- methyl]-2-methyl-propanethioamide 67 (S)-N-[[3-[3-[4- Same as above Z (c)(hydroxyacetyl)-1- piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]-methyl]cyclopropane- carbothioamide

When following the procedure of Example 28, step 3, an appropriateamount of the amine listed below is reacted with the dithio compoundlisted below, the respective compounds, Examples 68 to 78 of Table D areobtained.

TABLE D Example Dithio Compound No. Compound Amine (from Preparation Z)68 (S)-N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide, thiomorpholine S,S- dioxide

Z (a) 69 (S)-N-[[3-[3-Fluoro-4- Same as above Z (b) (4-thiomorpholinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide,thiomorpholine S,S-dioxide 70 (S)-N-[[3-[3-Fluoro-4- Same as above Z (c)(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-cyclopropanecarbothio- amide, thiomorpholine S,S-dioxide 71(S)-N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]- methyl]thioacetamide, thiomorpholine S,S- dioxide

Ethyl dithioacetate 72 (S)-N-[[3-[3,5-Difluoro- Same as above Z (a)4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-propanethioamide, thiomorpholine S,S- dioxide 73(S)-N-[[3-[3,5-Difluoro- Same as above Z (b) 4-(4-thiomorpholinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide,thiomorpholine S,S-dioxide 74 (S)-N-[[3-[3,5-Difluoro- Same as above Z(c) 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-cyclopropanecarbothio- amide, thiomorpholine S,S-dioxide 75(S)-N-[[3-[4-(4-thio- morpholinyl)phenyl]-2- oxo-5-oxazolidinyl]-methyl]thioacetamide, thiomorpholine S,S- dioxide

Ethyl dithioacetate 76 (S)-N-[[3-[4-(4-thio- Same as above Z (a)morpholinyl)phenyl]-2- oxo-5-oxazolidinyl]- methyl]propanethio- amide,thiomorpholine S,S-dioxide 77 (S)-N-[[3-[4-(4-thio- Same as above Z (b)morpholinyl)phenyl]-2- oxo-5-oxazolidinyl]- methyl]-2-methyl-propanethioamide, thiomorpholine S,S- dioxide 78 (S)-N-[[3-[4-(4-thio-Same as above Z (c) morpholinyl)phenyl]-2- oxo-5-oxazolidinyl]-methyl]cyclopropane- carbothioamide, thiomorpholine S,S- dioxide

When following the procedure of Example 26, an appropriate amount of theamine listed below is reacted with the dithio compound listed below therespective compounds, Examples 79 to 99 of Table E are obtained.

TABLE E Example Dithio Compound No. Compound Amine (See Preparation Z)79 (S)-N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide

Z (a) 80 (S)-N-[[3-[3-Fluoro-4- Same as above Z (b) (4-thiomorpholinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 81(S)-N-[[3-[3-Fluoro-4- Same as above Z (c) (4-thiomorpholinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl] cyclopropanecarbothioamide 82(S)-N-[[3-[3-Fluoro-4- Same as above Z (d) (4-thiomorpholinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]- butanethioamide 83(S)-N-[[3-[3-Fluoro-4- Same as above Z (e) (4-thiomorpholinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]-3- methylbutanethioamide 84(S)-N-[[3-[3-Fluoro-4- Same as above Z (f) (4-thiomorpholinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylbutanethioamide 85(S)-N-[[3-[3-Fluoro-4- Same as above Z (g) (4-thiomorpholinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]- 3,3-dimethylbutanethioamide 86(S)-N-[[3-[3-Fluoro-4- Same as above Z (h) (4-thiomorpholinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclobutanecarbothioamide 87(S)-N-[[3-[3-Fluoro-4- Same as above Z (i) (4-thiomorpholinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopentanecarbothioamide 88(S)-N-[[3-[3-Fluoro-4- Same as above Z (j) (4-thiomorpholinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclohexanecarbothioamide 89(S)-N-[[3-[3-5 Fluoro-4- Same as above Z (k) (4-thiomorpholinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopropylethanethioamide 90(S)-N-[[3-[3-Fluoro-4- Same as above Z (l) (4-thiomorpholinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclobutylethanethioamide 91(S)-N-[[3-[3-Fluoro-4- Same as above Z (m) (4-thiomorpholinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopentylethanethioamide 92(S)-N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- thioacetamide

Ethyl dithioacetate 93 (S)-N-[[3-[3,5-Difluoro- Same as above Z (a)4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-propanethioamide 94 (S)-N-[[3-[3,5-Difluoro- Same as above Z (b)4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-methylpropanethioamide 95 (S)-N-[[3-[3,5-Difluoro- Same as above Z (c)4-(4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-cyclopropanecarbothioamide 96 (S)-N-[[3-[4-(4-thio-morpholinyl)phenyl]-2- oxo-5-oxazolidinyl]- methyl]thioacetamide

Ethyl dithioacetate 97 (S)-N-[[3-[4-(4-thio- Same as above Z (a)morpholinyl)phenyl]-2- oxo-5-oxazolidinyl]- methyl]propanethioamide 98(S)-N-[[3-[4-(4-thio- Same as above Z (b) morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]-2-methyl- propanethioamide 99(S)-N-[[3-[4-(4-thio- Same as above Z (c) morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]cyclopropane- carbothioamide

The amine utilized in Examples 41 to 53 is prepared as described inExample 27, step 3. The amine utilized in Examples 54 to 57 is preparedby the procedure of Example 27, steps 1 to 3 by substituting theappropriate(S)-N-[[3-[3,5-difluoro4-(4-thio-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methanolfor compound 62 in step 1 of Example 27.

The amine utilized in Examples 58 to 61 is prepared by the procedure ofExample 27, steps 1 to 3 by substituting the appropriate(S)-N-[[3-[4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methanolfor compound 62 in Example 27, step 1. The appropriate oxazolidinylmethanol compound is obtained by following the procedure of Example 1 inU.S. Pat. No. 5,688,792, steps 1 through 3, only substituting4-fluoronitrobenzene for 3,4-difluoronitrobenzene in step 1 thereof.

The amine utilized in Examples 62 to 64 is prepared as compound 37 inExample 29 from the amide, 65, which is prepared as described in Example32 of U.S. Pat. No. 5,700,799. The amine utilized in Examples 65 to 67is prepared by the general procedure of Example 29 from the followingamide, the preparation of which is decribed in Example 3 of U.S. Pat.No. 5,700,799:

The amine utilized in Examples 68 to 70 is prepared as described in step2 of Example 28 above.

The amine utilized in Examples 71 to 74 is prepared as described inExample 28 by substituting(S)-N-[[3-[3,5-difluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methanolfor compound 62 in step I and following the procedure of steps 1 and 2.The appropriate oxazolidinyl methanol compound is prepared by followingthe general procedure of Example 4 of U.S. Pat. No. 5,688,792, steps 1through 4, only substituting thiomorpholine for morpholine in step 1thereof.

The amine utilized in Examples 75 to 78 is prepared as described inExample 28, step 1, above by substituting(S)-N-[3-[4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methanol forcompound 62 in step 1. The appropriate oxazolidinyl methanol is obtainedby following the procedure of Example 1 in U.S. Pat. No. 5,688,792,steps 1 through 3, only substituting 4-fluoronitrobenzene for3,4-difluoronitrobenzene in step 1 thereof.

The amine utilized in Examples 79 to 91 is prepared as described inExample 1, step 4, of U.S. Pat. No. 5,688,792. The amine utilized inExamples 92 to 95 is prepared as described in Example 4 of U.S. Pat. No.5,688,792 only substituting thiomorpholine for morpholine in step 1thereof. The amine utilized in Examples 96 to 99 is prepared by theprocedure of Example 1 of U.S. Pat. No. 5,688,792, only substituting4-fluoronitro-benzene for 3,4-difluoronitrobenzene in step 1 thereof.

EXAMPLE 100(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate,thiomorpholine S-oxide

A solution of 201 mg (0.554 mmol) of(S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)-phenyl]-2-oxo-5-oxazolidinyl]methyl]isothiocyanate,thiomorpholine s-oxide compound 82 from Example 33, step 1, in methanol(10 mL) is refluxed, under nitrogen for 18 hours and cooled. The solidis collected by filtration to give 0.138 g of the titled product. m.p.208-209° C.; Anal. calcd for C₁₆H₂₀FN₃O₄S₂: C, 47.87; H, 5.02; N, 10.47.Found: C, 47.81; H, 5.04: N, 10.49.

When in the procedure of Example 100 the thioisocyanate listed below issubstituted for compound 82 the products listed below as Examples 101 to109 are obtained.

TABLE F Isothiocyanate

Example Rc Ra Rb No. Compound OS F F 101(S)-N-[[3-[3,5-Difluoro-4-(4-thiomorpholinyl)-phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthio- carbamate,thiomorpholine S-oxide OS H H 102(S)-N-[[3-[4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate, thiomorpholine S-oxide O₂S HF 103 (S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthio- carbamate, thiomorpholineS,S-dioxide O₂S F F 104 (S)-N-[[3-[3,5-Difluoro-4-(4-thiomorpholinyl)-phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthio- carbamate,thiomorpholine S,S-dioxide O₂S H H 105(S)-N-[[3-[4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methyithiocarbamate, thiomorpholine S,S-dioxide SH F 106 (S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)-phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methyl- thiocarbamate S F F 107(S)-N-[[3-[3,5-Difluoro-4-(4-thiomorpholinyl)-phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methyl- thiocarbamate S H H 108(S)-N-[[3-[4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate

H H 109 (S)-N-[[3-(3-Fluoro-4-(4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- O-methylthiocarbamate

When in the procedure of Example 100 an appropriate amount of ethanoland isopropyl alcohol were substituted for methanol, the followingrespective compounds were obtained:

EXAMPLE 110

(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthiocarbamate,thiomorpholine S-oxide. m.p. 198-199° C.; Anal. calcd for C₁₇H₂₂FN₃O₄S₂:C, 49.14; H, 5.34; N, 10.11. Found: C, 49.06; H, 5.27; N, 10.10.

EXAMPLE 111

(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-isopropylthiocarbamate,thiomorpholine S-oxide. m.p. 180-181° C.; Anal. calcd for C₁₈H₂₄FN₃O₄S₂:C, 50.33; H, 5.63; N, 9.78. Found: C, 50.29; H, 5.69; N, 9.82.

When in the procedure of Example 114 an appropriate amount of(S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]isothiocyanateis substituted for compound 82 and ethanol or isopropyl alcohol issubstituted for methanol, the following respective products areobtained:

EXAMPLE 112(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthiocarbamateEXAMPLE 113(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-iso-propylthiocarbamateEXAMPLE 114(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N-methylthiourea,thiomorpholine S-oxide

A stirred suspension of 240 mg (0.650 mmol) of compound 82 from Example33, step 1 in THF (5 mL) at 0° C. is treated with a 2M solution ofmethylamine in THF (0.42 mL, 0.845 mmol) and kept at ambient temperaturefor 18 hours. The solid is collected by filtration to give 0.221 g ofthe titled product.

Following the procedure of Example 114, only substituting an appropriateamount of dimethylamine and azetidine for methylamine, the followingcompounds are obtained:

EXAMPLE 115

(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′-dimethylthiourea,thiomorpholine S-oxide; Anal. Calcd for C₁₇H₂₃FN₄O₃S₂, C, 49.26; H,5.59; N, 13.52. Found C, 49.11; H, 5.57; N, 13.40; mp 180-182° C.

EXAMPLE 116

(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamide,thiomorpholine S-oxide; Anal. Calcd for C₁₈H₂₃FN₄O₃S₂, C, 50.69; H,5.43; N, 13.14. Found: C, 50.79; H, 5.45; N, 12.82; mp 213-214° C.

When in the procedure of Example 114 an appropriate amount of(S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]isothiocyanateis substituted for compound 82, the following compound is obtained:

EXAMPLE 117(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]methyl-N′-methylthiourea

When in the procedure of Example 117 an appropriate amount ofdimethylamine and azetidine are substituted for methylamine, thefollowing respective products are obtained:

EXAMPLE 118(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′-dimethylthioureaEXAMPLE 119(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamide

When in the procedure of Example 33 an appropriate amount of compound 31from Example 26 is substituted for compound 33 and the general procedureof steps 1 and 2 of Example 33 are followed, the following compound isobtained.

EXAMPLE 120(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioureaEXAMPLE 121(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl-2-oxo-5-oxazolidinyl]methyl]propanethioamide

A stirred mixture of 200 mg (0.514 mmol) of 29 methyl dithiopropionate(247 mg, 2.06 mmol), triethylamine (0.58 mL, 4.11 mmol), THF (5.4 mL)and methylene chloride (5.4 mL) is kept, under nitrogen, for 3 days,diluted with water and extracted with methylene chloride. The extractsare dried (MgSO₄) and concentrated. Chromatography of the residue onsilica gel and crystallization of the product from methanol gives 0.132g of the titled product. m.p. 190-191° C.; Anal. calcd for C₁₉H₂₅FN₄O₄S:C, 53.76; H, 5.94; N, 13.20; S, 7.55. Found: C, 53.66; H, 5.94; N,13.20; S, 7.37.

Following the procedure of Example 121 only substituting dithiocompounds Z(b) to Z(m) from Preparation Z above for methyldithiopropionate, the following compounds are obtained.

TABLE G

Example No. Compound 122 (S)-N-[[3-[3-fluoro-4-[4-(hydroxyacetyl)-1- R =CH(CH₃)₂ piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]-methyl]-2-methylpropanethioamide; Anal. calcd for C₂₀H₂₇FN₄O₄S: C,54.78; H, 6.21; N, 12.78; S, 7.31. Found: C, 54.67; H, 6.34; N, 12.41;S, 7.15 123 (S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]cyclopropanecarbothioamide; mp 179- 181° C.; Anal. calcd forC₂₀H₂₅FN₄O₄S: C, 55.03; H, 5.77; N, 12.84; S, 7.34. Found: C, 55.15; H,5.72; N, 12.76; S, 7.09

124 (S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1- R = CH₂—CH₂—CH₃piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]butanethioamide 125(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]-3-methylbutanethioamide

126 (S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]-2-methylbutanethioamide

127 (S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1- R = CH₂—C(CH₃)₃piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]-3,3-dimethylbutanethioamide 128(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]cyclobutanecarbothioamide

129 (S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]cyclopentanecarbothioamide

130 (S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]cyclohexanecarbothioamide

131 (S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]-2-cyclopropylethanethioamide

132 (S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]-2-cyclobutylethanethioamide

133 (S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]-2-cyclopentylethanethioamide

When in the procedure of Example 100 an appropriate amount of compound80 from Example 31 is substituted for compound 82, and ethanol orisopropyl alcohol is substituted for methanol, the following respectivecompounds are obtained:

EXAMPLE 134(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthiocarbamateEXAMPLE 135(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-iso-propylthiocarbamateEXAMPLE 136(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′-methylthiourea

When in the procedure of Example 114 an appropriate amount of compound80 from Example 31 is substituted for compound 82, the title compound isobtained.

Following the procedure of Example 114 only substituting an appropriateamount of compound 80 from Example 31 for compund 82 and substituting anappropriate amount of dimethylamine and azetidine for methylamnine, thefollowing compounds, Examples 137 and 138, are obtained:

EXAMPLE 137(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′-dimethylthioureaEXAMPLE 138(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamideEXAMPLE 139(S)-N-[[3-[3,5-Difluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate

Part A: Following the procedure of Example 33, step 1, only substitutingan appropriate amount of compound 37 from Example 29, step 5, forcompound 33,(S)-N-[[3,5-[3-difluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]isothiocyanateis obtained.

Part B: Upon substitution of an appropriate amount of(S)-N-[[3-[3,5-difluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]isothiocyanatefor compound 82 in the general procedure of Example 100, the titlecompound is obtained.

EXAMPLE 140(S)-N-[[3-[4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate

Part A: Following the procedure of Example 33, step 1, only substitutingan appropriate amount of(S)-N-[[3-[4-[4-hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]aminefor compound 33,(S)-N-[[3-[4-[4(hydroxyacetyl)-1-piperainyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]isothiocyanateis obtained.

Part B: Upon substituting an appropriate amount of(S)-N-[[3-[4-[4-(hydroxy-acetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]isothiocyanatefor compound 82 in the general procedure of Example 100, the titlecompound is obtained.

EXAMPLE 141(S)-N-[[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide

An ice cold, stirred solution of 30.4 g (70.8 mmol) of starting material58 from Example 25, step 1), and triethylamine (15.4 mL, 110 mmol) inmethylene chloride (2570 mL) is treated with m-nitrobenzenesulfonylchloride (18.8 g, 84.9 mmol) and kept, under nitrogen, at ambienttemperature (24° C.) for 24 hours. Additional m-nitrobenzenesulfonylchloride (1.88 g) and triethylamine (1.54 mL) are added and the mixtureis kept for one additional day at ambient temperature, washed withwater, saturated sodium bicarbonate and brine, dried (Na₂SO₄) andconcentrated to give an oily product, 85. The alcohol, 58 is preparedaccording to the procedures of Brickner (J. Med. Chem. 1996, 39,673-679), see compound 5a therein.

A stirred mixture of 85, acetonitrile (1270 mL), isopropanol (1270 mL)and ammonium hydroxide (1270 mL) is kept at ambient temperature for 3days and concentrated in vacuo. Chromatography of the residue on silicagel with 0.5% NH₄OH-1% MeOH—CH₂Cl₂ gives 22.4 g of the amine, 86.

An ice cold, stirred solution of the amine 86 in THF (650 mL) istreated, during 20 mintues with a solution of di-tert-butyl dicarbonate(12.0 g, 55.2 mmol) in THF (90 mL). The mixture is kept at ambienttemperature for 18 hours and concentrated in vacuo. The residue,dissolved in methylene chloride, is washed with dilute sodiumbicarbonate, dried (MgSO₄) and concentrated. Crystallization of theresidue from methanol-ethyl acetate gives 20.0 g of the Boc protectedamine. Additional product (4.1 g) is obtained by chromatographing themother liquors on silica gel with 1-2% methanol-methylene chloride.

A solution of the protected amine, 87, (5.00 g, 9.46 mmol) in ethanol(150 mL) is treated with 10% palladium-on-carbon catalyst (1.0 g) andhydrogenated at an initial pressure of 30 psi for 3 hours. The catalystis removed by filtration through Celite and the filtrate wasconcentrated to give 3.66 g of compound 88.

A stirred solution of compound 88 (1.10 g, 2.79 mmol) in pyridine (10mL) is treated with acetic anhydride (289 μL, 3.07 mmol), kept atambient temperature for 2 hours and concentrated in vacuo. A solution ofthe residue in methylene chloride is washed with dilute hydrochloricacid, dried (MgSO₄) and concentrated to give 1.23 g of compound 89: MSm/z 436 (M⁺).

An ice cold, stirred 4N solution of HCl in dioxane (10 mL) is treatedwith compound 89 (1.10 g, 2.52 mmol). The mixture is kept in the icebath for 30 minutes and at ambient temperature for 1 hour. It was thenmixed with methylene chloride and concentrated. The residue istriturated with methylene chloride to give 1.03 g of the aminehydrochloride.

A stirred mixture of compound P-90 (250 mg), triethylamine (0.75 mL,5.36 mmol), to ethyl dithioacetate (307 μL, 2.68 mmol), methylenechloride (7.4 mL) and THF (7.4 mL) is kept at ambient temperature for 1day, concentrated and chromatographed on silica gel with mixtures ofmethanol-methylene chloride containing 1-2% methanol. Crystallization ofthe product from ethyl acetate-heptane gives 0.160 g of the titledproduct: Anal. calcd for C₁₈H₂₃FN₄O₃S: C, 54.8 1; H, 5.88; N, 14.20; S,8.13. Found: C, 54.92; H, 5.95; N, 14.08; S, 7.94; mp 158° C.

When in the general procedure of Example 141 an appropriate amount of

is substituted for compound 58 and the procedure of steps 1 through 6are followed, the respective amine compounds P-91 and P-92 listed beloware obtained:

The alcohols above designated as x and y are prepared according to theprocedures of Brickner (J. Med. Chem., 1996, 39, 673-679), bysubstituting an appropriate amount of 2,6-difluoro-4-nitrobenzene(trifluoromethane) sulfonate and 4-fluoronitrobenzene respectively for3,4-difluoronitrobenzene in the preparation of 2a therein.

When in the procedure of Example 141 an appropriate amount of x or y issubstituted for compound 58 and the procedures of steps 1 through 4 arefollowed, the following Boc protected compounds listed below areobtained.

When in the procedure of Example 141, step 5, an appropriate amount ofcompound 88, compound x-b or compound y-b is treated with the reagentlisted below and the general procedures of step 5 and step 6 arefollowed, the amines listed below as Preparation P-93 through P-128 areobtained.

The amine compound set forth below as P-129 is obtained by refluxing for6 days a solution of compound 88 (1.00 g, 2.54 mmol), sulfamide (305 mg,3.18 mmol) and 1,2-dimethyoxyethane (6 mL). The solid which precipitatesis collected by filtration and chromatographed on silica gel with 5%methanol-methylene chloride. Crystallization of the product frommethanol-methylene chloride gives 0.551 g of the sulfamoyl derivative,which is used in step 6 of Example 141 to give P-129. When compounds x-band y-b are substituted for compound 88 and this general procedure isfollowed, Preparations P-130 and P-131 respectively set forth below areobtained.

Following the general procedures of steps 5 and 6 of Example 141 only instep 5 substituting chloroacetonitrile or 2-fluoroethyl bromiderespectively for acetic anhydride and using potassium carbonate inacetonitrile, and using either compound 88, compound x-b or compoundy-b, the respective amines set forth below as Preparations P-132 toP-137 are obtained.

The amine compound set forth below as Preparation P-138 is obtained bycombining compound 88 (1.10 g, 2.75 mmol) set forth in step 5 of Example141 with N-formylbenzotriazole (493 mg, 3.35 mmol) in THF (30 mL) andthe mixture is kept at ambient temperature for 18 hours. The mixture isconcentrated and the residue in methylene chloride is washed with 1Nsodium hydroxide and dilute sodium chloride, dried (MgSO₄),concentrated, and chromatographed on silica gel with mixtures ofmethanol and methylene chloride containing 1-2% methanol to give 1.09 gof the N-formyl derivative which is utilized in the general procedure ofstep 6 of Example 141 to give Preparation P-138. When in this foregoingprocedure compound x-b or compound y-b is substituted for compound 88,Preparations P-139 and and P-140 as set forth below are obtained.

Boc Preparation Reagent Compound R R″ R′ No. methoxyacetylchloride 88x-b y-b

H F H F F H P-93 P-94 P-95 cyanoacetyl chloride 88 x-b y-b

H F H F F H P-96 P-97 P-98 acetoxyacetyl chloride 88 x-b y-b

H F H F F H P-99 P-100 P-101 benzyloxyacetyl chloride 88 x-b y-b

H F H F F H P-102 P-103 P-104 methyl chloroformate 88 x-b y-b

H F H F F H P-105 P-106 P-107 methanesulfonyl chloride 88 CH₃SO₂— H FP-108 x-b F F P-109 y-b H H P-110 ethanesulfonyl chloride 88 CH₃CH₂SO₂—H F P-111 x-b F F P-112 y-b H H P-113 chloromethanesulfonyl 88 ClCH₂SO₂—H F P-114 chloride x-b F F P-115 y-b H H P-116 cyanomethanesulfonyl 88NCCH₂SO₂— H F P-117 chloride x-b F F P-118 y-b H H P-119N-methylsulfamoyl 88 CH₃NHSO₂— H F P-120 chloride x-b F F P-121 y-b H HP-122 N,N-dimethylsulfamoyl 88 (CH₃)₂NSO₂— H F P-123 chloride x-b F FP-124 y-b H H P-125 ethyl chloroformate 88 x-b y-b

H F H F F H P-126 P-127 P-128 sulfamide 88 H₂NSO₂— H F P-129 x-b F FP-130 y-b H H P-131 chloroacetonitrile 88 NCCH₂— H F P-132 x-b F F P-133y-b H H P-134 2-fluoroethyl bromide 88 FCH₂CH₂— H F P-135 x-b F F P-136y-b H H P-137 N-formylbenzotriazole 88 x-b y-b

H F H F F H P-138 P-139 P-140

EXAMPLES 142-161

When following the general procedures of Example 141, step 7, anappropriate amount of the amine listed below and the dithio compoundfrom Preparation Z listed below are utilized, the respective productsdesignated as Examples 142 to 400 in Table H are obtained.

TABLE H Example Dithio No. Product Amine Compound 142(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 Z (a)piperazinyl)phenyl]-2-oxo-5-oxazo- lidinyl]methyl]propanethioamide; mp161-162° C.; Anal. calcd for C₁₉H₂₅FN₄O₃S: C, 55.87; H, 6.17; N, 13.72;S, 7.85. Found: C, 55.79; H, 6.26; N, 13.60; S, 7.71 143(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 Z (b)piperazinyl)phenyl]-2-oxo-5-oxazo- lidinyl]methyl]-2-methylpropane-thioamide 144 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 Z (c)piperazinyl)phenyl]-2-oxo-5-oxazo- lidinyl]methyl]cyclopropanecarbo-thioamide; mp 159-160° C.; Anal. calcd for C₂₀H₂₅FN₄O₃S: C, 57.13; H,5.99; N, 13.32; S, 7.62. Found: C, 57.05; H, 6.01; N, 13.15; S, 7.45.145 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 Z (d)piperazinyl)phenyl]-2-oxo-5-oxazo- lidinyl]methyl]butanethioamide 146(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 Z (e)piperazinyl)phenyl]-2-oxo-5-oxazo- lidinyl]methyl]-3-methylbutane-thioamide 147 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 Z (f)piperazinyl)phenyl]-2-oxo-5-oxazo- lidinyl]methyl]-2-methylbutane-thioamide 148 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 Z (g)piperazinyl)phenyl]-2-oxo-5-oxazo- lidinyl]methyl]-3,3-dimethylbutane-thioamide 149 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 Z (h)piperazinyl)phenyl]-2-oxo-5-oxazo- lidinyl]methyl]cyclobutanecarbo-thioamide 150 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 Z (i)piperazinyl)phenyl]-2-oxo-5-oxazo- lidinyl]methyl]cyclopentanecarbo-thioamide 151 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 Z (j)piperazinyl)phenyl]-2-oxo-5-oxazo- lidinyl]methyl]cyclohexanecarbo-thioamide 152 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 Z (k)piperazinyl)phenyl]-2-oxo-5-oxazo- lidinyl]methyl]-2-cyclopropylethane-thioamide 153 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 Z (l)piperazinyl)phenyl]-2-oxo-5-oxazo- lidinyl]methyl]-2-cyclobutylethane-thioamide 154 (S)-N-[[3-(3-Fluoro-4-(4-acetyl-1- P-90 Z (m)piperazinyl)phenyl]-2-oxo-5-oxazo- lidinyl]methyl]-2-cyclopentylethane-thioamide 155 (S)-N-[[3-[3,5-Difluoro-4-(4-acetyl-1- P-91 Ethylpiperazinyl)phenyl]-2-oxo-5-oxazo- dithio- lidinyl]methyl]thioacetamideacetate 156 (S)-N-[[3-[3,5-Difluoro-4-(4-acetyl-1- P-91 Z (a)piperazinyl)phenyl]-2-oxo-5-oxazo- lidinyl]methyl]propane- thioamide 157(S)-N-[[3-[3,5-Difluoro-4-(4-acetyl-1- P-91 Z (b)piperazinyl)phenyl]-2-oxo-5-oxazo- lidinyl]methyl]-2-methyl-propanethioamide 158 (S)-N-[[3-[3,5-Difluoro-4-(4-acetyl-1- P-91 Z (c)piperazinyl)phenyl]-2-oxo-5-oxazo- lidinyl]methyl]cyclopropane-carbothioamide 159 (S)-N-[[3-[4-(4-Acetyl-1- P-92 Ethylpiperazinyl)phenyl]-2-oxo-5- dithio- oxazolidinyl]methyl]thioacetamideacetate 160 (S)-N-[[3-[4-(4-Acetyl-1- P-92 Z (a)piperazinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]propane- thioamide 161(S)-N-[[3-[4-(4-Acetyl-1- P-92 Z (b) piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methyl- propanethioamide 162(S)-N-[[3-[4-(4-Acetyl-1- P-92 Z (c) piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropane- carbothioamide 163(S)-N-[[3-[3-Fluoro-4-[4- P-93 Ethyl (methoxyacetyl)-1-piperazinyl]-dithio- phenyl]-2-oxo-5-oxazolidinyl]- acetate methyl]thioacetamide 164(S)-N-[[3-[3-Fluoro-4-[4- P-93 Z (a) (methoxyacetyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-propanethioamide 165(S)-N-[[3-[3-Fluoro-4-[4- P-93 Z (b) (methoxyacetyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-2-methylpropanethioamide 166(S)-N-[[3-[3-Fluoro-4-[4- P-93 Z (c) (methoxyacetyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyI]- methyl]-cyclopropanecarbothioamide 167(S)-N-[[3-[3-Fluoro-4-[4- P-93 Z (d) (methoxyacetyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-butanethioamide 168(S)-N-[[3-[3-Fluoro-4-[4- P-93 Z (e) (methoxyacetyl)-l-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-3-methylbutanethioamide 169(S)-N-[[3-[3-Fluoro-4-[4- P-93 Z (f) (methoxyacetyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-2-methylbutanethioamide 170(S)-N-[[3-[3-Fluoro-4-[4- P-93 Z (g) (methoxyacetyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-3,3-dimethylbutanethioamide 171(S)-N-[[3-[3-Fluoro-4-[4- P-93 Z (h) (methoxyacetyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-cyclobutanecarbothioamide 172(S)-N-[[3-[3-Fluoro-4-[4- P-93 Z (i) (methoxyacetyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-cyclopentanecarbothioamide 173(S)-N-[[3-[3-Fluoro-4-[4- P-93 Z (j) (methoxyacetyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-cyclohexanecarbothioamide 174(S)-N-[[3-[3-Fluoro-4-[4- P-93 Z (k) (methoxyacetyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-2-cyclopropyle- thanethioamide175 (S)-N-[[3-[3-Fluoro-4-[4- P-93 Z (l) (methoxyacetyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-2-cyclobutylethanethioamide 176(S)-N-[[3-[3-Fluoro-4-[4- P-93 Z (m) (methoxyacetyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-2-cyclopentylethane- thioamide177 (S)-N-[[3-[3,5-Difluoro-[4-[4- P-94 Ethyl(methoxyacetyl)-1-piperazinyl]- dithio- phenyl]-2-oxo-5-oxazolidinyl]-acetate methyl]-thioacetamide 178 (S)-N-[[3-[3,5-Difluoro-[4-[4- P-94 Z(a) (methoxyacetyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]-methyl]-propanethioamide 179 (S)-N-[[3-[3,5-Difluoro-[4-[4- P-94 Z (b)(methoxyacetyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]-methyl]-2-methylpropanethioamide 180 (S)-N-[[3-[3,5-Difluoro-[4-[4- P-94Z (c) (methoxyacetyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]-methyl]-cyclopropanecarbothioamide 181(S)-N-[[3-[4-[4-(methoxyacetyl)-1- P-95 Ethelpiperazinyl]phenyl]-2-oxo-5-oxazo- dithio- lidinyl]methyl]thioacetamideacetate 182 (S)-N-[[3-[4-[4-(methoxyacetyl)-1- P-95 Z (a)piperazinyl]phenyl]-2-oxo-5-oxazo- lidinyl]methyl]propanethioamide 183(S)-N-[[3-[4-[4-(methoxyacetyl)-1- P-95 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazo- lidinyl]methyl]-2-methylpropane-thioamide 184 (S)-N-[[3-[4-[4-(methoxyacetyl)-1- P-95 Z (c)piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]cyclopropane-carbothioamide 185 (S)-N-[[3-[3-Fluoro-4-[4-(cyano- P-96 Ethelacetyl)-1-piperazinyl]-phenyl]-2-oxo- dithio-5-oxazolidinyl]methyl]thioacetamide acetate 186(S)-N-[[3-[3-Fluoro-4-[4-(cyano- P-96 Z (a)acetyl)-1-piperazinyl]-phenyl]-2-oxo- 5-oxazolidinyl]methyl]propanethio-amide 187 (S)-N-[[3-[3-Fluoro-4-[4-(cyano- P-96 Z (b)acetyl)-1-piperazinyl]-phenyl]-2-oxo- 5-oxazolidinyl]methyl]-2-methyl-propanethioamide 188 (S)-N-[[3-[3-Fluoro-4-[4-(cyano- P-96 Z (c)acetyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropane- carbothioamide 189(S)-N-[[3-[3,5-Difluoro-4-[4-(cyano- P-97 Ethelacetyl)-1-piperazinyl]phenyl]-2-oxo- dithio-5-oxazolidinyl]-methyl]thioacetamide acetate 190(S)-N-[[3-[3,5-Difluoro-4-[4-(cyano- P-97 Z (a)acetyl)-1-piperazinyl]phenyl]-2-oxo- 5-oxazolidinyl]-methyl]propane-thioamide 191 (S)-N-[[3-[3,5-Difluoro-4-[4-(cyano- P-97 Z (b)acetyl)-1-piperazinyl]phenyl]-2-oxo- 5-oxazolidinyl]methyl]-2-methyl-propanethioamide 192 (S)-N-[[3-[3,5-Difluoro-4-[4-(cyano- P-97 Z (c)acetyl)-1-piperazinyl]phenyl]-2-oxo- 5-oxazolidinyl]methyl]cyclopropane-carbothioamide 193 (S)-N-[[3-[4-[4-(Cyano- P-98 Ethylacetyl)-1-piperazinyl]phenyl]-2- dithio- oxo-5-oxazolidinyl]methyl]-acetate thioacetamide 194 (S)-N-[[3-[4-[4-(Cyanoacetyl)-1- P-98 Z (a)piperazinyl]phenyl]-2-oxo-5-oxazo- lidinyl]methyl]propanethioamide 195(S)-N-[[3-[4-[4-(Cyanoacetyl)-1- P-98 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazoli- dinyl]methyl]-2-methylpropane-thioamide 196 (S)-N-[[3-[4-[4-(Cyanoacetyl)-1- P-98 Z (c)piperazinyl]phenyl]-2-oxo-5-oxazo- lidinyl]methyl]cycopropanecarbothio-amide 197 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxy- P-99 Ethylacetyl)-1-piperazinyl]phenyl]-2-oxo- dithio- 5-oxazolidinyl]methyl]-acetate thioacetamide 198 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxy- P-99 Z (a)acetyl)-1-piperazinyl]phenyl]-2-oxo- 5-oxazolidinyl]methyl]-propanethioamide 199 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxy- P-99 Z (b)acetyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 200 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxy- P-99 Z (c)acetyl)-1-piperazinyl]phenyl]-2-oxo- 5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 201 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxy- P-99 Z(d) acetyl)-1-piperazinyl]phenyl]-2-oxo- 5-oxazolidinyl]methyl]-butanethioamide 202 (S)-N-[[3-[3-Fluoro-4-(4-(acetoxy- P-99 Z (e)acetyl)-1-piperazinyl]phenyl]-2-oxo- 5-oxazolidinyl]methyl]-3-methylbutanethioamide 203 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxy- P-99 Z (f)acetyl)-l-piperazinyl]phenyl]-2-oxo- 5-oxazolidinyl]methyl]-2-methylbutanethioamide 204 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxy- P-99 Z (g)acetyl)-1-piperazinyl]phenyl]-2-oxo- 5-oxazolidinyl]methyl]-3,3-dimethylbutanethioamide 205 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxy- P-99 Z(h) acetyl)-1-piperazinyl]phenyl]-2-oxo- 5-oxazolidinyl]methyl]-cyclobutanecarbothioamide 206 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxy- P-99 Z(i) acetyl)-1-piperazinyl]phenyl]-2-oxo- 5-oxazolidinyl]methyl]-cyclopentanecarbothioamide 207 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxy- P-99 Z(j) acetyl)-1-piperazinyl]phenyl]-2-oxo- 5-oxazolidinyl]methyl]-cyclohexanecarbothioamide 208 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxy- P-99 Z(k) acetyl)-1-piperazinyl]phenyl]-2-oxo- 5-oxazolidinyl]methyl]-2-cyclopropylethanethioamide 209 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxy- P-99 Z(l) acetyl)-1-piperazinyl]phenyl]-2-oxo- 5-oxazolidinyl]methyl]-2-cyclobutylethanethioamide 210 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxy- P-99 Z(m) acetyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-2-cyclopentylethanethioamide 211 (S)-N-[[3-[3,5-Difluoro-4-[4- P-99 Ethyl(acetoxyacetyl)-1-piperazinyl]- dithio- phenyl]-2-oxo-5-oxazolidinyl]-acetate methyl]-thioacetamide 212 (S)-N-[[3-[3,5-Difluoro-4- P-100 Z (a)[4-(acetoxyacetyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]-methyl]-propanethioamide 213 (S)-N-[[3-[3,5-Difluoro-4-[4- P-100 Z (b)(acetoxyacetyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]-methyl]-2-methylpropanethioamide 214 (S)-N-[[3-[3,5-Difluoro-4- P-100 Z(c) [4-(acetoxyacetyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]-methyl]-cyclopropanecarbothioamide 215 (S)-N-[[3-[4-[4-(Acetoxy- P-100Ethyl acetyl)-1-piperazinyl]phenyl]- dithio-2-oxo-5-oxazolidinyl]methyl]- acetate thioacetamide 216(S)-N-[[3-[4-[4-(Acetoxy- P-101 Z (a) acetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 217(S)-N-[[3-[4-[4-(Acetoxyacetyl)-1- P-101 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazo- lidinyl]methyl]-2-methylpropane-thioamide 218 (S)-N-[[3-[4-[4-(Acetoxyacetyl)-1- P-101 Z (c)piperazinyl]phenyl]-2-oxo-5-oxazo- lidinyl]methyl]cyclopropanecarbo-thioamide 219 (S)-N-[[3-[3-Fluoro-4-[4-(benzyl- P-102 Ethyloxyacetyl)-1-piperazinyl]phenyl]-2- dithio- oxo-5-oxazolidinyl]methyl]-acetate thioacetamide 220 (S)-N-[[3-[3-Fluoro-4-[4-(benzyl- P-102 Z (a)oxyacetyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-propanethioamide 221 (S)-N-[[3-[3-Fluoro-4-(4-(benzyl- P-102 Z (b)oxyacetyl)-1-piperazinyl]phenyI]-2- oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 222 (S)-N-[[3-[3-Fluoro-4-(4-benzyl- P-102 Z (c)oxyacetyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyI]-cyclopropanecarbothioamide 223 (S)-N-[[3-[3,5-Difluoro-4-[4- P-103 Ethyl(benzyloxyacetyl)-1-piperazinyi]- dithio- phenyl]-2-oxo-5-oxazolidinyl]-acetate methyl]-thioacetamide 224 (S)-N-[[3-[3,5-Difluoro-4-[4- P-103 Z(a) (benzyloxyacetyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]-methyl]-propanethioamide 225 (S)-N-[[3-[3,5-Difluoro-4-[4- P-103 Z (b)(benzyloxyacetyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]-methyl]-2-methylpropanethioamide 226 (S)-N-[[3-[3,5-Difluoro-4-[4- P-103Z (c) (benzyloxyacetyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]-methyl]-cyclopropanecarbothioamide 227 (S)-N-[[3-[3-Fluoro-4-[4- P-105Ethyl (methoxycarbonyl)-1-piperazinyl]- dithio-phenyl]-2-oxo-5-oxazolidinyl]- acetate methyl]-thioacetamide 228(S)-N-[[3-[3-Fluoro-4-[4- P-105 Z (a) (methoxycarbonyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-propanethioamide 229(S)-N-[[3-[3-Fluoro-4-[4- P-105 Z (b) (methoxycarbonyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-2-methylpropanethioamide 230(S)-N-[[3-[3-Fluoro-4-[4- P-105 Z (c) (methoxycarbonyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-cyclopropanecarbothioamide 231(S)-N-[[3-[3-Fluoro-4-[4- P-105 Z (d) (methoxycarbonyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-butanethioamide 232(S)-N-[[3-[3-Fluoro-4-[4- P-105 Z (e) (methoxycarbonyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-3-methylbutanethioamide 233(S)-N-[[3-[3-Fluoro-4-[4- P-105 Z (f) (methoxycarbonyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-2-methylbutanethioamide 234(S)-N-[[3-[3-Fluoro-4-[4- P-105 Z (g) (methoxycarbonyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-3,3-dimethylbutanethioamide 235(S)-N-[[3-[3-Fluoro-4-[4- P-105 Z (h) (methoxycarbonyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-cyclobutanecarbo- thioamide 236(S)-N-[[3-[3-Fluoro-4-[4- P-105 Z (i) (methoxycarbonyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-cyclopentanecarbothioamide 237(S)-N-[[3-[3-Fluoro-4-[4- P-105 Z (j) (methoxycarbonyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-cyclohexanecarbothioamide 238(S)-N-[[3-[3-Fluoro-4-[4- P-105 Z (k) (methoxycarbonyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-2-cyclopropylethane- thioamide239 (S)-N-[[3-[3-Fluoro-4-[4- P-105 Z (l)(methoxycarbonyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]-methyl]-2-cyclobutylethane- thioamide 240 (S)-N-[[3-[3-Fluoro-4-[4-P-105 Z (m) (methoxycarbonyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-2-cyclopentylethane- thioamide241 (S)-N-[[3-[3,5-Difluoro-4-[4- P106 Ethyl(methoxycarbonyl)-1-piperazinyl]- dithio- phenyl]-2-oxo-5-oxazolidinyl]-acetate methyl]-thioacetamide 242 (S)-N-[[3-[3,5-Difluoro-4-[4- P106 Z(a) (methoxycarbonyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]-methyl]-propanethioamide 243 (S)-N-[[3-[3,5-Difluoro-4-[4- P106 Z (b)(methoxycarbonyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]-methyl]-methylpropanethioamide 244 (S)-N-[[3-[3,5-Difluoro-4-[4- P106 Z(c) (methoxycarbonyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]-methyl]-cyclopropanecarbo- thioamide 245(S)-N-[[3-[4-[4-(methoxycarbonyl)-1- P-107 Ethylpiperazinyl]phenyl]-2-oxo-5-oxazo- dithio- lidinyl]methyl]-thioacetamideacetate 246 (S)-N-[[3-[4-[4-(methoxycarbonyl)-1- P-107 Z (a)piperazinyl]phenyl]-2-oxo-5-oxazo- lidinyl]methyl]-propanethioamide 247(S)-N-[[3-[4-[4-(methoxycarbonyl)-1- P-107 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazo- lidinyl]methyl]-2-methyl-propanethioamide 248 (S)-N-[[3-[4-[4-(methoxycarbonyl)-1- P-107 Z (c)piperazinyl]phenyl]-2-oxo-5-oxazo- lidinyl]methyl]-cyclopropanecarbo-thioamide 249 (S)-N-[[3-[3-Fluoro-4-[4-methane- P-108 Ethylsulfonyl)-1-piperazinyl]phenyl]-2- dithio-oxo-5-oxazolidinyl]methyl]-thioacet- acetate amide; mp 197-198° C.;Anal. calcd for C₁₇H₂₃FN₄O₄S₂: C, 47.43; H, 5.39; N, 13.01; S, 14.89.Found: C, 47.25; H, 5.40; N, 12.82; S, 14.56. 250(S)-N-[[3-[3-Fluoro-4-[4-methane- P-108 Z (a)sulfonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-propane-thioamide; mp 207-208° C.; Anal. calcd for C₁₈H₂₅FN₄O₄S₂: C, 48.63; H,5.67; N, 12.60; S, 14.42. Found: C, 48.51; H, 5.59; N, 12.52; S, 14.09.251 (S)-N-[[3-[3-Fluoro-4-[4-methane- P-108 Z (b)sulfonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-2-methyl-propanethioamide; mp 204-206° C.; Anal. calcd for C₁₉H₂₇FN₄O₄S₂: C,49.76; H, 5.93; N, 12.22; S, 13.98. Found: C, 49.63; H, 5.92; N, 14.14;S, 13.91. 252 (S)-N-[[3-[3-Fluoro-4-[4-methane- P-108 Z (c)sulfonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-cyclo-propanecarbothioamide; mp 197-198° C.; Anal. calcd for C₁₉H₂₅FN₄O₄S₂: C,49.98; H, 5.52; N, 12.27; S, 14.04. Found: C, 49.42; H, 5.50; N, 12.08;S, 13.80. S, 14.56. 253 (S)-N-[[3-[3,5-Difluoro-4-[4-(meth- P-109 Ethylanesulfonyl)-1-piperazinyl]phenyl]- dithio-2-oxo-5-oxazolidinyl]methyl]- acetate thioacetamide 254(S)-N-[[3-[3,5-Difluoro-4-[4-(meth- P-109 Z (a)anesulfonyl)-1-piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]methyl]-propanethioamide 255 (S)-N-[[3-[3,5-Difluoro-4-[4-(meth- P-109 Z (b)anesulfonyl)-1-piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 256 (S)-N-[[3-[3,5-Difluoro-4-[4-(meth- P-109 Z(c) anesulfonyl)-1-piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 257 (S)-N-[[3-[4-[4-(methanesulfonyl)-1 P-110Ethyl piperazinyl]phenyl]-2-oxo-5-oxazoli- dithio-dinyl]methyl]-thioacetamide acetate 258(S)-N-[[3-[4-[4-(methanesulfonyl)-1 P-110 Z (a)piperazinyl]phenyl]-2-oxo-5-oxazoli- dinyl]methyl]-propanethioamide 259(S)-N-[[3-[4-[4-(methanesulfonyl)-1 P-110 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazoli- dinyl]methyl]-2-methylpropane-thioamide 260 (S)-N-[[3-[4-[4-(methanesulfonyl)-1 P-110 Z (c)piperazinyl]phenyl]-2-oxo-5-oxazoli- dinyl]methyl]-cyclopropanecarbo-thioamide 261 (S)-N-[[3-[3-Fluoro-4-[4-(ethane- P-111 Ethylsulfonyl)-1-piperazinyl]phenyl]-2- dithio- oxo-5-oxazolidinyl]methyl]-acetate thioacetamide 262 (S)-N-[[3-[3-Fluoro-4-[4-(ethane- P-111 Z (a)sulfonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-propanethioamide 263 (S)-N-[[3-[3-Fluoro-4-[4-(ethane- P-111 Z (b)sulfonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 264 (S)-N-[[3-[3-Fluoro-4-[4-(ethane- P-111 Z(c) sulfonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 265 (S)-N-[[3-[3,5-Difluoro-4-[4- P-112 Ethyl(ethanesulfonyl)-1-piperazinyl]- dithio- phenyl]-2-oxo-5-oxazolidinyl]-acetate methyl]-thioacetamide 266 (S)-N-[[3-[3,5-Difluoro-4-[4- P-112 Z(a) (ethanesulfonyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]-methyl]-propanethioamide 267 (S)-N-[[3-[3,5-Difluoro-4-[4- P-112 Z (b)(ethanesulfonyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]-methyl]-2-methylpropanethioamide 268 (S)-N-[[3-[3,5-Difluoro-4-[4- P-112Z (c) (ethanesulfonyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]-methyl]-cyclopropanecarbothioamide 269(S)-N-[[3-[4-[4-(ethanesulfonyl)-1- P-113 Ethylpiperazinyl]phenyl]-2-oxo-5-oxazo- dithio- lidinyl]methyl]thioacetamideacetate 270 (S)-N-[[3-[4-[4-(ethanesulfonyl)-1- P-113 Z (a)piperazinyl]phenyl]-2-oxo-5-oxazo- lidinyl]methyl]propanethioamide 271(S)-N-[[3-[4-[4-(ethanesulfonyl)-1- P-113 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazo- lidinyl]methyl]-2-methylpropane-thioamide 272 (S)-N-[[3-[4-[4-(ethanesulfonyl)-1- P-113 Z (c)piperazinyl]phenyl]-2-oxo-5-oxazo- lidinyl]methyl]cyclopropanecarbo-thioamide 273 (S)-N-[[3-[3-Fluoro-4-[4-(chloro- P-114 Ethylmethanesulfonyl)-1-piperazinyl]- dithio- phenyl]-2-oxo-5-oxazolidinyl]-acetate methyl]-thioacetamide 274 (S)-N-[[3-[3-Fluoro-4-[4-(chloro-P-114 Z (a) methanesulfonyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-propanethioamide 275(S)-N-[[3-[3-Fluoro-4-[4-(chloro- P-114 Z (b)methanesulfonyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]-methyl]-2-methylpropanethioamide 276 (S)-N-[[3-[3-Fluoro-4-[4-(chloro-P-114 Z (c) methanesulfonyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-cyclopropanecarbothioamide 277(S)-N-[[3-[3,5-Difluoro-4-[4-(chloro- P-115 Ethylmethanesulfonyl)-1-piperazinyl]- dithio- phenyl]-2-oxo-5-oxazolidinyl]-acetate methyl]-thioacetamide 278 (S)-N-[[3-[3,5-Difluoro-4-[4-(chloro-P-115 Z (a) methanesulfonyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-propanethioamide 279(S)-N-[[3-[3,5-Difluoro-4-[4-(chloro- P-115 Z (b)methanesulfonyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]-methyl]-2-methylpropanethioamide 280(S)-N-[[3-[3,5-Difluoro-4-[4-(chloro- P-115 Z (c)methanesulfonyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]-methyl]-cyclopropanecarbothioamide 281(S)-N-[[3-[4-[4-(chloromethanesul- P-116 Ethylfonyl)-1-piperazinyl]phenyl]-2-oxo- dithio- 5-oxazolidinyl]methyl]-acetate thioacetamide 282 (S)-N-[[3-[4-[4-(chloromethanesul- P-116 Z (a)fonyl)-1-piperazinyl]phenyl]-2-oxo- 5-oxazolidinyl]methyl]-propanethioamide 283 (S)-N-[[3-[4-[4-(chloromethanesul- P-116 Z (b)fonyl)-1-piperazinyl]phenyl]-2-oxo- 5-oxazolidinyl]methyl]-2-methylpropanethioamide 284 (S)-N-[[3-[4-[4-(chloromethanesul- P-116 Z(c) fonyl)-1-piperazinyl]phenyl]-2-oxo- 5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 285 (S)-N-[[3-[3-Fluoro-4-[4-(cyano- P-117Ethyl methane-sulfonyl)-1-piperazinyl]- dithio-phenyl]-2-oxo-5-oxazolidinyl]- acetate methyl]-thioacetamide 286(S)-N-[[3-[3-Fluoro-4-[4-(cyano- P-117 Z (a)methane-sulfonyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]-methyl]-propanethioamide 287 (S)-N-[[3-[3-Fluoro-4-[4-(cyano- P-117 Z(b) methane-sulfonyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]-methyl]-2-methylpropanethioamide 288 (S)-N-[[3-[3-Fluoro-4-[4-(cyano-P-117 Z (c) methane-sulfonyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-cyclopropanecarbothioamide 289(S)-N-[[3-[3,5-Difluoro-4-[4-(cyano- P-118 Ethylmethane-sulfonyl)-1-piperazinyl]- dithio- phenyl]-2-oxo-5-oxazolidinyl]-acetate methyl]thioacetamide 290 (S)-N-[[3-[3,5-Difluoro-4-[4-(cyano-P-118 Z (a) methane-sulfonyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]propanethioamide 291(S)-N-[[3-[3,5-Difluoro-4-[4-(cyano- P-118 Z (b)methane-sulfonyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]-methyl]-2-methylpropanethioamide 292(S)-N-[[3-[3,5-Difluoro-4-[4-(cyano- P-118 Z (c)methane-sulfonyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]-methyl]cyclopropanecarbothioamide 293 (S)-N-[[3-[4-[4-(Cyanomethane-P-119 Ethyl sulfonyl)-1-piperazinyl]phenyl]- dithio-2-oxo-5-oxazolidinyl]methyl]- acetate thioacetamide 294(S)-N-[[3-[4-[4-(Cyanomethane- P-119 Z (a)sulfonyl)-1-piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]methyl]-propanethioamide 295 (S)-N-[[3-[4-[4-(Cyanomethane- P-119 Z (b)sulfonyl)-1-piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 296 (S)-N-[[3-[4-[4-(Cyanomethane- P-119 Z (c)sulfonyl)-1-piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 297 (S)-N-[[3-[3-Fluoro-4-[4-(N-methyl- P-120Ethyl sulfamoyl)-1-piperazinyl]phenyl]- dithio-2-oxo-5-oxazolidinyl]methyl]- acetate thioacetamide 298(S)-N-[[3-[3-Fluoro-4-[4-(N-methyl- P-120 Z (a)sulfamoyl)-1-piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]methyl]-propanethioamide 299 (S)-N-[[3-[3-Fluoro-4-[4-(N-methyl- P-120 Z (b)sulfamoyl)-1-piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 300 (S)-N-[[3-[3-Fluoro-4-[4-(N-methyl- P-120 Z(c) sulfamoyl)-1-piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 301 (S)-N-[[3-[3,5-Difluoro-4-[4-(N- P-121Ethyl methylsulfamoyl)-1-piperazinyl]- dithio-phenyl]-2-oxo-5-oxazolidinyl]- acetate methyl]thioacetamide 302(S)-N-[[3-[3,5-Difluoro-4-[4-(N- P-121 Z (a)methylsulfamoyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]-methyl]propanethioamide 303 (S)-N-[[3-[3,5-Difluoro-4-[4-(N- P-121 Z (b)methylsulfamoyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]-methyl]-2-methylpropanethioamide 304 (S)-N-[[3-[3,5-Difluoro-4-[4-(N-P-121 Z (c) methylsulfamoyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]cyclopropanecarbothioamide 305(S)-N-[[3-[4-[4-(N-methylsulfamoyl)- P-122 Ethyl1-piperazinyl]phenyl]-2-oxo-5-oxazo- dithio-lidinyl]methyl]-thioacetamide acetate 306(S)-N-[[3-[4-[4-(N-methylsulfamoyl)- P-122 Z (a)1-piperazinyl]phenyl]-2-oxo-5-oxazo- lidinyl]methyl]-propanethioamide307 (S)-N-[[3-[4-[4-(N-methylsulfamoyl)- P-122 Z (b)1-piperazinyl]phenyl]-2-oxo-5-oxazo- lidinyl]methyl]-2-methyl-propanethioamide 308 (S)-N-[[3-[4-[4-(N-methylsulfamoyl)- P-122 Z (c)1-piperazinyl]phenyl]-2-oxo-5-oxazo- lidinyl]methyl]-cyclopropane-carbothioamide 309 (S)-N-[[3-[3-Fluoro-4-[4-(N,N- P-123 Ethyldimethylsulfamoyl)-1-piperazinyl]- dithio-phenyl]-2-oxo-5-oxazolidinyl]- acetate methyl]-thioacetamide 310(S)-N-[[3-[3-Fluoro-4-[4-(N,N- P-123 Z (a)dimethylsulfamoyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]-methyl]-propanethioamide 311 (S)-N-[[3-[3-Fluoro-4-[4-(N,N- P-123 Z (b)dimethylsulfamoyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]-methyl]-2-methylpropanethioamide 312 (S)-N-[[3-[3-Fluoro-4-[4-(N,N-P-123 Z (c) dimethylsulfamoyl)-1-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]- methyl]-cyclopropanecarbothioamide 313(S)-N-[[3-[3,5-Difluoro-4-[4- P-124 Ethyl (N,N-dimethylsulfamoyl)-1-dithio- piperazinyl]-phenyl]-2-oxo-5-oxazo- acetatelidinyl]-methyl]-thioacetamide 314 (S)-N-[[3-[3,5-Difluoro-4-[4- P-124 Z(a) (N,N-dimethylsulfamoyl)-1-piper- azinyl]-phenyl]-2-oxo-5-oxazoli-dinyl]-methyl]-propanethioamide 315 (S)-N-[[3-[3,5-Difluoro-4-[4- P-124Z (b) (N,N-dimethylsulfamoyl)-1-piper- azinyl]-phenyl]-2-oxo-5-oxazo-lidinyl]-methyl]-2-methylpropane- thioamide 316(S)-N-[[3-[3,5-Difluoro-4-[4- P-124 Z (c)(N,N-dimethylsulfamoyl)-1-piper- azinyl]-phenyl]-2-oxo-5-oxazo-lidinyl]-methyl]-cyclopropane- carbothioamide 317(S)-N-[[3-[4-[4-(N,N-dimethylsul- P-125 Ethylfamoyl)-1-piperazinyl]phenyl]-2-oxo- dithio- 5-oxazolidinyl]methyl]-acetate thioacetamide 318 (S)-N-[[3-[4-[4-(N,N-dimethylsul- P-125 Z (a)famoyl)-1-piperazinyl]phenyl]-2-oxo- 5-oxazolidinyl]methyl]-propanethioamide 319 (S)-N-[[3-[4-[4-(N,N-dimethylsul- P-125 Z (b)famoyl)-1-piperazinyl]phenyl]-2-oxo- 5-oxazolidinyl]methyl]-2-methylpropanethioamide 320 (S)-N-[[3-[4-[4-(N,N-dimethylsul- P-125 Z(c) famoyl)-1-piperazinyl]phenyl]-2-oxo- 5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 321 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxy- P-126Ethyl carbonyl)-1-piperazinyl]phenyl]-2- dithio-oxo-5-oxazolidinyl]methyl]- acetate thioacetamide 322(S)-N-[[3-[3-Fluoro-4-[4-(ethoxy- P-126 Z (a)carbonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-propanethioamide 323 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxy- P-126 Z (b)carbonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 324 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxy- P-126 Z(c) carbonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 325 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxy- P-126 Z(d) carbonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-butanethioamide 326 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxy- P-126 Z (e)carbonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-3-methylbutanethioamide 327 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxy- P-126 Z(f) carbonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-methylbutanethioamide 328 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxy- P-126 Z (g)carbonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-dimethylbutanethioamide 329 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxy- P-126 Z(h) carbonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-cyclobutanecarbothioamide 330 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxy- P-126 Z(i) carbonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-cyclopentanecarbothioamide 331 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxy- P-126 Z(j) carbonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-cyclohexanecarbothioamide 332 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxy- P-126 Z(k) carbonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-2-cyclopropylethanethioamide 333 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxy- P-126Z (l) carbonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-2-cyclobutylethanethioamide 334 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxy- P-126Z (m) carbonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-2-cyclopentylethanethioamide 335 (S)-N-[[3-[3,5-Difluoro-4-[4-(ethoxy-P-127 Ethyl carbonyl)-1-piperazinyl]phenyl]-2- dithio-oxo-5-oxazolidinyl]methyl]- acetate thioacetamide 336(S)-N-[[3-[3,5-Difluoro-4-[4-(ethoxy- P-127 Z (a)carbonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-propanethioamide 337 (S)-N-[[3-[3,5-Difluoro-4-[4-(ethoxy- P-127 Z (b)carbonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 338 (S)-N-[[3-[3,5-Difluoro-4-[4-(ethoxy- P-127Z (c) carbonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 339 (S)-N-[[3-[4-[4-(ethoxycarbonyl)- P-128Ethyl 1-piperazinyl]-phenyl]-2-oxo-5- dithio-oxazolidinyI]methyl]thioacetamide acetate 340(S)-N-[[3-[4-[4-(ethoxycarbonyl)- P-128 Z (a)1-piperazinyl]-phenyl]-2-oxo-5- oxazolidinyI]methyl]propane- thioamide341 (S)-N-[[3-[4-[4-(ethoxycarbonyl)- P-128 Z (b)1-piperazinyl]-phenyl]-2-oxo-5- oxazolidinyI]methyl]2-methylpro-panethioamide 342 (S)-N-[[3-[4-[4-(ethoxycarbonyl)- P-128 Z (c)1-piperazinyl]-phenyl]-2-oxo-5- oxazolidinyI]methyl]cyclopro-panecarbothioamide 343 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl- P-129 Ethyl1-piperazinyl)-phenyl]-2-oxo-5- dithio- oxaxolidinyl]methyl]- acetatethioacetamide 344 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl- P-129 Z (a)1-piperazinyl)-phenyl]-2-oxo-5- oxaxolidinyl]methyl]propane- thioamide345 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl- P-129 Z (b)1-piperazinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-methyl-propanethioamide 346 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl- P-129 Z (c)1-piperazinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]-cyclo-propanecarbothioamide 347 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl- P-129 Z(d) 1-piperazinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]butane-thioamide 348 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl- P-129 Z (e)1-piperazinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]-3-methyl-butanethioamide 349 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl- P-129 Z (f)1-piperazinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-methyl-butanethioamide 350 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl- P-129 Z (g)1-piperazinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]-3,3-dimethyl-butanethioamide 351 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl- P-129 Z (h)1-piperazinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]cyclo-butanecarbothioamide 352 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl- P-129 Z (i)1-piperazinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]cyclo-pentanecarbothioamide 353 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl- P-129 Z(j) 1-piperazinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]cyclo-hexanecarbothioamide 354 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl- P-129 Z (k)1-piperazinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-cyclo-propylethanethioamide 355 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl- P-129 Z(l) 1-piperazinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-cyclo-butylethanethioamide 356 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl- P-129 Z (m)1-piperazinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-cyclo-pentylethanethioamide 357 (S)-N-[[3-[3,5-Difluoro-4-(4-sul- P-130 Ethylfamoyl-1-piperazinyl)phenyl]-2-oxo- dithio- 5-oxazolidinyl]methyl]-acetate thioacetamide 358 (S)-N-[[3-[3,5-Difluoro-4-(4-sul- P-130 Z (a)famoyl-1-piperazinyl)phenyl]-2-oxo- 5-oxazolidinyl]methyl]propane-thioamide 359 (S)-N-[[3-[3,5-Difluoro-4-(4-sul- P-130 Z (b)famoyl-1-piperazinyl)phenyl]-2-oxo- 5-oxazolidinyl]methyl]-2-methylpropanethioamide 360 (S)-N-[[3-[3,5-Difluoro-4-(4-sul- P-130 Z (c)famoyl-1-piperazinyl)phenyl]-2-oxo- 5-oxazolidinyl]methyl]cyclopropane-carbothioamide 361 (S)-N-[[3-[4-(4-sulfamoyl-1- P-131 Ethylpiperazinyl)phenyl]-2-oxo-5-oxa- dithio- zolidinyl]methyl]- acetatethioacetamide 362 (S)-N-[[3-[4-(4-sulfamoyl-1- P-131 Z (a)piperazinyl)phenyl]-2-oxo-5-oxa- zolidinyl]methyl]- propanethioamide 363(S)-N-[[3-[4-(4-sulfamoyl-1- P-131 Z (b)piperazinyl)phenyl]-2-oxo-5-oxa- zolidinyl]methyl]-2-methylpropanethioamide 364 (S)-N-[[3-[4-(4-sulfamoyl-1- P-131 Z (c)piperazinyl)phenyl]-2-oxo-5-oxa- zolidinyl]methyl]-cyclopropanecarbothioamide 365 (S)-N-[[3-[3-Fluoro-4-[4-(cyano- P-132Ethyl methyl)-1-piperazinyl]phenyl]-2- dithio-oxo-5-oxazolidinyl]methyl]- acetate thioacetamide 366(S)-N-[[3-[3-Fluoro-4-[4-(cyano- P-132 Z (a)methyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-propanethioamide 367 (S)-N-[[3-[3-Fluoro-4-[4-(cyano- P-132 Z (b)methyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 368 (S)-N-[[3-[3-Fluoro-4-[4-(cyano- P-132 Z(c) methyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 369 (S)-N-[[3-[3,5-Difluoro-4-[4- P-133 Ethyl(cyanomethyl)-1-piperazinyl]phenyl]- dithio-2-oxo-5-oxazolidinyl]methyl]- acetate thioacetamide 370(S)-N-[[3-[3,5-Difluoro-4-[4- P-133 Z (a)(cyanomethyl)-1-piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]methyl]-propanethioamide 371 (S)-N-[[3-[3,5-Difluoro-4-[4- P-133 Z (b)(cyanomethyl)-1-piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 372 (S)-N-[[3-[3,5-Difluoro-4-[4- P-133 Z (c)(cyanomethyl)-1-piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 373 (S)-N-[[3-[4-[4-(cyanomethyl)-1- P-134Ethyl piperazinyl]phenyl]-2-oxo-5-oxazo- dithio-lidinyl]methyl]thioacetamide acetate 374(S)-N-[[3-[4-[4-(cyanomethyl)-1- P-134 Z (a)piperazinyl]phenyl]-2-oxo-5-oxazo- lidinyl]methyl]propanethioamide 375(S)-N-[[3-[4-[4-(cyanomethyl)-1- P-134 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazo- lidinyl]methyl]-2-methylpropane-thioamide 376 (S)-N-[[3-[4-[4-(cyanomethyl)-1- P-134 Z (c)piperazinyl]phenyl]-2-oxo-5-oxazo- lidinyl]methyl]cyclopropane-carbothioamide 377 (S)-N-[[3-[3-Fluoro-4-[4-(2-fluoro- P-135 Ethylethyl)-1-piperazinyl]phenyl]-2-oxo-5- dithio- oxazolidinyl]methyl]-acetate thioacetamide 378 (S)-N-[[3-[3-Fluoro-4-[4-(2-fluoro- P-135 Z(a) ethyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-propanethioamide 379 (S)-N-[[3-[3-Fluoro-4-[4-(2-fluoro- P-135 Z (b)ethyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-methylpropanethioamide 380 (S)-N-[[3-[3-Fluoro-4-[4-(2-fluoro- P-135 Z(c) ethyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-cyclopropanecarbothioamide 381 (S)-N-[[3-[3,5-Difluoro-4-[4- P-136 Ethyl(2-fluoroethyl)-1-piperazinyl]phenyl]- dithio-2-oxo-5-oxazolidinyl]methyl]- acetate thioacetamide 382(S)-N-[[3-[3,5-Difluoro-4-[4- P-136 Z (a)(2-fluoroethyl)-1-piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]methyl]-propanethioamide 383 (S)-N-[[3-[3,5-Difluoro-4-[4- P-136 Z (b)(2-fluoroethyl)-1-piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 384 (S)-N-[[3-[3,5-Difluoro-4-[4- P-136 Z (c)(2-fluoroethyl)-1-piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 385 (S)-N-[[3-[4-[4-(2-fluoroethyl)-1- P-137Ethyl piperazinyl]phenyl]-2-oxo-5-oxazo- dithio-lidinyl]methyl]thioacetamide acetate 386(S)-N-[[3-[4-[4-(2-fluoroethyl)-1- P-137 Z (a)piperazinyl]phenyl]-2-oxo-5-oxazo- lidinyl]methyl]propane- thioamide 387(S)-N-[[3-[4-[4-(2-fluoroethyl)-1- P-137 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazo- lidinyl]methyl]-2-methylpropane-thioamide 388 (S)-N-[[3-[4-[4-(2-fluoroethyl)-1- P-137 Z (c)piperazinyl]phenyl]-2-oxo-5-oxazo- lidinyl]methyl]cyclopropane-carbothioamide 389 (S)-N-[[3-[3-Fluoro-4-(4-formyl-1- P-138 Ethylpiperazinyl)phenyl]-2-oxo-5-oxazo- dithio- lidinyl]methyl]- acetatethioacetamide; Anal calcd for C₁₇H₂₁FN₄O₃S: C, 53.67; H, 5.56; N, 14.73;S, 8.43. Found: C, 53.14; H, 5.42; N, 14.25; S, 8.18. 390(S)-N-[[3-[3-Fluoro-4-(4-formyl-1- P-138 Z (a)piperazinyl)phenyl]-2-oxo-5-oxazo- lidinyl]methyl]- propanethioamide; mp166-167° C.; Anal. calcd for C₁₈H₂₃FN₄O₃S: C, 54.81; H, 5.88; N, 14.20;S, 8.13. Found: C, 54.83; H, 6.00; N, 14.12; S, 7.96. 391(S)-N-[[3-[3-Fluoro-4-(4-formyl-1- P-138 Z (b)piperazinyl)phenyl]-2-oxo-5-oxazo- lidinyl]methyl]-2-methyl-propanethioamide; mp 157-158° C.; Anal. calcd for C₁₉H₂₅FN₄O₃S: C,55.87; H, 6.17; N, 13.72; S, 7.85. Found: C, 55.67; H, 6.19; N, 13.50;S, 7.70. 392 (S)-N-[[3-[3-Fluoro-4-(4-formyl-1- P-138 Z (c)piperazinyl)phenyl]-2-oxo-5-oxazo- lidinyl]methyl]-cyclopropanecarbothioamide; mp 178-179° C.; Anal. calcd forC₁₉H₂₃FN₄O₃S: C, 56.14; H, 5.70; N, 13.78; S, 7.89. Found: C, 56.13; H,5.64; N, 13.64; S, 7.75. 393 (S)-N-[[3-[3,5-Difluro-4-(4-formyl- P-139Ethyl 1-piperazinyl)-phenyl]-2-oxo-5- dithio- oxazolidinyl]methyl]-acetate thioacetamide 394 (S)-N-[[3-[3,5-Difluro-4-(4-formyl- P-139 Z(a) 1-piperazinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]propane-thioamide 395 (S)-N-[[3-[3,5-Difluro-4-(4-formyl- P-139 Z (b)1-piperazinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-methyl-propanethioamide 396 (S)-N-[[3-[3,5-Difluro-4-(4-formyl- P-139 Z (c)1-piperazinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]cyclo-propanecarbothioamide 397 (S)-N-[[3-[4-(4-formyl-1- P-140 Ethylpiperazinyl)phenyl]-2-oxo-5- dithio- oxazolidinyl]methyl]- acetatethioacetamide 398 (S)-N-[[3-[4-(4-formyl-1- P-140 Z (a)piperazinyl)phenyl]-2-oxo-5-oxazo- lidinyl]methyl]propanethioamide 399(S)-N-[[3-[4-(4-formyl-1- P-140 Z (b) piperazinyl)phenyl]-2-oxo-5-oxazo-lidinyl]methyl]-2-methylpro- panethioamide 400 (S)-N-[[3-[4-(4-formyl-1-P-140 Z (c) piperazinyl)phenyl]-2-oxo-5-oxazo-lidinyl]methyl]cyclopropane- carbothioamide

When in the general procedure of Example 31, step 1, an appropriateamount of the amine listed below is substituted for compound 33, theisothiocyanate corresponding to the amines P-90, P-93, P-99, P-105,P-126 and P-129 are obtained.

When in the general procedure of Example 114 an appropriate amount ofthe isothiocyanate and the amine listed below are substituted forcompound 82 and methylamine, the respective products listed below areobtained.

TABLE I Isothiocyanate Example Corresponding No. Product to Amine No.Amine 401 (S)-N-[[3-[3-Fluoro-4- P-90  methylamine(4-acetyl-1-piperazinyl) phenyl]-2-oxo-5- oxazolidinyl]-methyl]-N′-methylthiourea 402 (S)-N-[[3-[3-Fluoro-4- P-90  dimethylamine(4-acetyl-1-piperazinyl) phenyl]-2-oxo-5- oxazolidinyl]-methyl]-N′,N′-dimethylthiourea 403 (S)-N-[[3-[3-Fluoro-4- P-90  azetidine(4-acetyl-1-piperazinyl) phenyl]-2-oxo-5- oxazolidinyl]-methyl]-1-azetidinecarbothioamide 404 (S)-N-[[3-[3-Fluoro-4- P-90  anhydrous(4-thiomorpholinyl)- ammonia phenyl]-2-oxo-5- oxazolidinyl]-methyl]-thiourea 405 (S)-N-[[3-[3-Fluoro-4- P-93  methylamine[4-(methoxyacetyl)-1- piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]-methyl]-N′- methylthiourea 406 (S)-N-[[3-[3-Fluoro-4- P-93 dimethylamine [4-(methoxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-N′, N′-dimethylthiourea 407(S)-N-[[3-[3-Fluoro-4- P-93  azetidine [4-(methoxyacetyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl] methyl]-1-azetidine-carbothioamide 408 (S)-N-[[3-[3-Fluoro-4- P-99  methylamine[4-(acetoxyacetyl)-1- piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]-methyl]-N′- methylthiourea 409 (S)-N-[[3-[3-Fluoro-4- P-99 dimethylamine [4-(acetoxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-N′, N′-dimethylthiourea 410(S)-N-[[3-[3-Fluoro-4- P-99  azetidine [4-(acetoxyacetyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]- methyl]-1-azetidine-carbothioamide 411 (S)-N-[[3-[3-Fluoro-4- P-105 methylamine[4-(methoxycarbonyl)- 1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]-methyl]-N′- methylthiourea 412 (S)-N-[[3-[3-Fluoro-4- P-105dimethylamine [4-(methoxycarbonyl)- 1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-N′,N′- dimethylthiourea 413(S)-N-[[3-[3-Fluoro-4- P-105 azetidine [4-(methoxycarbonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]- methyl]-1-azetidine-carbothioamide 414 (S)-N-[[3-[3-Fluoro-4- P-126 methylamine[4-(ethoxycarbonyl)-1- piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]-methyl]-N′- methylthiourea 415 (S)-N-[[3-[3-Fluoro-4- P-126dimethylamine [4-(ethoxycarbonyl)-1- piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-N′, N′-dimethylthiourea 416(S)-N-[[3-[3-Fluoro-4- P-126 azetidine [4-(ethoxycarbonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]- methyl]-1-azetidine-carbothioamide 417 (S)-N-[[3-[3-Fluoro-4- P-129 methylamine(4-sulfamoyl-1- piperazinyl)phenyl]-2- oxo-5-oxazolidinyl]- methyl]-N′-methylthiourea 418 (S)-N-[[3-[3-Fluoro-4- P-129 dimethylamine(4-sulfamoyl-1- piperazinyl)phenyl]-2- oxo-5-oxazolidinyl]- methyl]-N′-N′-dimethylthiourea 419 (S)-N-[[3-[3-Fluoro-4- P-129 azetidine(4-sulfamoyl-1- piperazinyl)phenyl]-2- oxo-5-oxazolidinyl]-methyl]-N′-azetidine- carbothioamide

When in the general procedure of Example 100 an appropriate amount ofthe isothiocyanate and alcohol listed below are utilized in the samemanner as Compound 82 and methanol are utilized, the respective productslisted below are obtained.

TABLE J Isothiocyanate Example Corresponding No. Product to Amine No.Amine 420 (S)-N-[[3-[3-Fluoro-4- P-90  methanol (4-acetyl-1-piperazinyl)phenyl]-2- oxo-5-oxazolidinyl]- methyl]-O-methyl-thiocarbamate 421 (S)-N-[[3-[3-Fluoro-4- P-90  ethanol (4-acetyl-1-piperazinyl)phenyl]-2- oxo-5-oxazolidinyl]- methyl]-O-ethyl-thiocarbamate 422 (S)-N-[[3-[3-Fluoro-4- P-90  isopropyl (4-acetyl-1-alcohol piperazinyl)phenyl]-2- oxo-5-oxazolidinyl]- methyl]-O-iso-propylthiocarbamate 423 (S)-N-[[3-[3-Difluoro-4- P-91  methanol(4-acetyl-1- piperazinyl)phenyl]-2- oxo-5-oxazolidinyl]-methyl]-O-methyl- thiocarbamate 424 (S)-N-[[3-[4-(4-Acetyl-1- P-92 methanol piperazinyl)phenyl]-2- oxo-5-oxazolidinyl]- methyl]-O-methyl-thiocarbamate 425 (S)-N-[[3-[3-Fluoro-4- P-93  methanol[4-(methoxyacetyl)-1- piperazinyl)phenyl]-2- oxo-5-oxazolidinyl]-methyl]-O-methyl- thiocarbamate 426 (S)-N-[[3-[3-Fluoro-4- P-93  ethanol[4-(methoxyacetyl)-1- piperazinyl)phenyl]-2- oxo-5-oxazolidinyl]-methyl]-O- ethylthiocarbamate 427 (S)-N-[[3-[3-Fluoro-4- P-93  isopropyl[4-(methoxyacetyl)-1- alcohol piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-iso- propylthiocarbamate 428(S)-N-[[3-[3,5-Difluoro- P-94  methylaminel [4-[4-(methoxy-acetyl)-1-piperazinyl] phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthiocarbamate 429 (S)-N-[[3-[4-[4- P-95 methylamine(methoxyacetyl)-1- piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]methyl]-O-methyl- thiocarbamate 430 (S)-N-[3-[3-Fluoro-4- P-96 methanol[4-(cyanoacetyl)-1- piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]-methyl]-O- methylthiocarbamate 431 (S)-N-[[3-[3,5-Difluoro- P-97 methanol 4-[4-(cyanoacetyl)-1- piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O- methylthiocarbamate 432(S)-N-[[3-[4-[4- P-98  methanol (Cyanoacetyl)-1- piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O- methylthiocarbamate 433(S)-N-[[3-[3-Fluoro-4- P-99  methanol [4-(acetoxyacetyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 434 (S)-N-[[3-[3-Fluoro-4- P-99  ethanol[4-(acetoxyacetyl)-1- piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]-methyl]-O- ethylthiocarbamate 435 (S)-N-[[3-[3-Fluoro-4- P-99  isopropyl[4-(acetoxyacetyl)-1- alcohol piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-iso- propylthiocarbamate 436(S)-N-[[3-[3,5-Difluoro- P-100 methanol 4-[4-(acetoxyacetyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]- methyl]-O-methyl-thiocarbamate 437 (S)-N-[[3-[4-[4- P-101 methanol (Acetoxyacetyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]- methyl]-O-methyl-thiocarbamate 438 (S)-N-[[3-[3-Fluoro-4- P-102 methanol[4-(benzyloxyacetyl)- 1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]-methyl]-O-methyl- thiocarbamate 439 (S)-N-[[3-[3,5-Difluoro- P-103methanol 4-[4-(benzyloxy- acetyl)-1-piperazinyl] phenyl]-2-oxo-5-oxazolidinyl]methyl]- O-methylthiocarbamate 440 (S)-N-[[3-[3-Fluoro-4-P-105 methanol [4-(methoxycarbonyl)- 1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O- methylthiocarbamate 441(S)-N-[[3-[3-Fluoro-4- P-105 ethanol [4-(methoxycarbonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]- methyl]-O-ethylthiocarbamate 442 (S)-N-[[3-[3-Fluoro-4- P-105 isopropyl[4-(methoxycarbonyl)- alcohol 1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O- iso-propylthiocarbamate 443(S)-N-[[3-[3,5-Difluoro- P-106 methanol 4-[4-(methoxycarbonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl] methyl]-O-methylthiocarbamate 444 (S)-N-[[3-[4-[4- P-107 methanol(methoxycarbonyl)-1- piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]-methyl]-O-methyl- thiocarbamate 445 (S)-N-[[3-[3-Fluoro-4- P-108methanol [4-(methanesulfonyl)- 1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O- methylthiocarbamate 446(S)-N-[[3-[3,5-Difluoro- P-109 methanol 4-[4-(methanesulfonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl] methyl]-O-methylthiocarbamate 447 (S)-N-[[3-[4-[4- P-110 methanol(methanesulfonyl)-1- piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]-methyl]-O-methyl- thiocarbamate 448 (S)-N-[[3-[3-Fluoro-4- P-111methanol [4-(ethanesulfonyl)-1- piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methyl- thiocarbamate 449(S)-N-[[3-[3,5-Difluoro- P-112 methanol 4-[4-(ethanesulfonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl] methyl]cyclopropane-carbothioamide 450 (S)-N-[[3-[4-[4- P-113 methanol (ethanesulfonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl] methyl]-O-methylthiocarbamate 451 (S)-N-[[3-[3-Fluoro- P-114 methanol4-[4-(chloromethane- sulfonyl)-1-piperazinyl] phenyl]-2-oxo-5-oxazolidinyl]methyl]- O-methylthiocarbamate 452 (S)-N-[[3-[3,5-Difluoro-P-115 methanol 4-[4-(chloromethane- sulfonyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazoli- dinyl]methyl]-O-methyl- thiocarbamate 453(S)-N-[[3-[4-[4- P-116 methanol (chloromethanesulfonyl)-1-piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl] methyl]-O-methylthiocarbamate 454 (S)-N-[[3-[3-Fluoro-4- P-117 methanol[4-(cyanomethane- sulfonyl)-1-piperazinyl] phenyl]-2-oxo-5-oxazolidinyl]methyl]- O-methylthiocarbamate 455 (S)-N-[[3-[3,5-Difluoro-P-118 methanol 4-[4-(cyanomethane- sulfonyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- O-methylthiocarbamate 456(S)-N-[[3-[4-[4- P-119 methanol (Cyanomethanesulfonyl)-1-piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 457 (S)-N-[[3-[3-Fluoro- P-120 methanol4-[4-(N-methylsulfa- moyl)-1-piperazinyl] phenyl]-2-oxo-5-oxazoli-dinyl]methyl]-O- methylthiocarbamate 458 (S)-N-[[3-[3,5-Difluoro- P-121methanol 4-[4-(N-methylsulfa- moyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazoli- dinyl]methyl]-O- methylthiocarbamate 459(S)-N-[[3-[4-[4- P-122 methanol (N-methylsulfamoyl)-1-piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 460 (S)-N-[[3-[3-Fluoro-4- P-123 methanol[4-(N,N-dimethylsulfa- moyl)-1-piperazinyl] phenyl]-2-oxo-5-oxazoli-dinyl]methyl]-O- methylthiocarbamate 461 (S)-N-[[3-[3,5-Difluoro- P-124methanol 4-[4-(N,N-dimethylsulfa- moyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazoli- dinyl]methyl]-O- methylthiocarbamate 462(S)-N-[[3-[4-[4- P-125 methanol (N,N-dimethylsulfa- moyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazoli- dinyl]methyl]-O- methylthiocarbamate 463(S)-N-[[3-[3-Fluoro- P-126 methanol 4-[4-(ethoxycarbonyl)-1-piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 464 (S)-N-[[3-[3-Fluoro- P-126 ethanol4-[4-(ethoxycarbonyl)-1- piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]-methyl]-O- ethylthiocarbamate 465 (S)-N-[[3-[3-Fluoro- P-126 isopropyl4-[4-(ethoxycarbonyl)-1- alcohol piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-iso- propylthiocarbamate 466(S)-N-[[3-[3,5-Difluoro- P-127 methanol 4-[4-(ethoxycarbonyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl] methyl]-O-methylthiocarbamate 467 (S)-N-[[3-[4-[4- P-128 methanol(ethoxycarbonyl)-1- piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]-O- methylthiocarbamate 468 (S)-N-[[3-[3-Fluoro-4- P-129 methanol(4-sulfamoyl-1- piperazinyl)phenyl]- 2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate, 469 (S)-N-[[3-[3-Fluoro- P-129 ethanol4-(4-sulfamoyl-1- piperazinyl)phenyl]-2- oxo-5-oxazolidinyl] methyl]-O-ethylthiocarbamate 470 (S)-N-[[3-[3-Fluoro- P-129 isopropyl4-(4-sulfamoyl-1- alcohol piperazinyl)phenyl]-2- oxo-5-oxazolidinyl]-methyl]-O-iso- propylthiocarbamate 471 (S)-N-[[3-[3,5-Difluoro- P-130methanol 4-(4-sulfamoyl-1- piperazinyl)phenyl]-2- oxo-5-oxazolidinyl]methyl]-O- methylthiocarbamate 472 (S)-N-[[3-[4-(4- P-131 methanolsulfamoyl-1-piperazinyl)- phenyl]-2-oxo-5-oxazoli- dinyl]methyl]-O-methylthiocarbamate 473 (S)-N-[[3-[3-Fluoro- P-132 methanol4-[4-(cyanomethyl)-1- piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]-methyl]-O- methylthiocarbamate 474 (S)-N-[[3-[3,5-Difluoro- P-133methanol 4-[4-(cyanomethyl)-1- piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O- methylthiocarbamate 475 (S)-N-[[3-[4-[4-P-134 methanoll (cyanomethyl)-1-piper- azinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]- O-methylthiocarbamate 476 (S)-N-[[3-[3-Fluoro-P-135 methanol 4-[4-(2-fluoroethyl)-1- piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O- methylthiocarbamate 477(S)-N-[[3-[3,5-Difluoro- P-136 methanol 4-[4-(2-fluoroethyl)-1-piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 478 (S)-N-[[3-[4-[4-(2- P-137 methanolfluoroethyl)-1- piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate 479 (S)-N-[[3-[3-Fluoro- P-138 methanol4-(4-formyl-1-piper- azinyl)phenyl]-2-oxo- 5-oxazolidinyl]- methyl]-O-methylthiocarbamate 480 (S)-N-[[3-[3,5-Difluro- P-139 methanol4-(4-formyl-1-piper- azinyl)phenyl]-2-oxo- 5-oxazolidinyl]- methyl]-O-methylthiocarbamate 481 (S)-N-[[3-[4-(4- P-140 methanolformyl-1-piperazinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthiocarbamate

EXAMPLE 482(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-tiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidiny]methyl]thioacetamide,thiazepine S-oxide

Step 1. Rexahydro-5-oxo-1,4-thiazepine is prepared according to theprocedure described by Gallego (J. Org. Chem. 1993, 58, 3905-3911).

Step 2. Lithium aluminum hydride (5.5 mL of a 1M solution in THF) isadded dropwise to a stirred solution of hexahydro-5-oxo-1,4-thiazepine(721.5 mg) in dry THF (21 mL) cooled to 0° C. The reaction mixture isstirred at 0° C. for 10 min, then at room temperature for 4 h. Thereaction mixture is quenched by careful successive addition of water(0.2 mL), 5 N aqueous NaOH (0.2 mL) and water (0.74 mL). The reactionmixture becomes very thick and gel-like. The reaction mixture is dilutedwith ether (50 mL) and filtered through a pad of celite. The filter cakeis washed with ether (100 mL). The filtrate is concentrated to afford616.6 mg of 1,4-hexahydrothiazepine which is used immediately in thenext step.

Step 3. To a stirred solution of 1,4-hexahydrothiazepine (596.0 mg) and3,4-difluoronitrobenzene (0.51 mL) in acetonitrile (14 mL) is addeddiisopropylethylamine (1.0 mL). The yellow solution is heated at refluxfor 18 h, then cooled and concentrated. The residue is diluted withCH₂Cl₂ (100 mL) and washed with saturated aqueous NH₄Cl (35 mL). Thephases are separated and the organics are dried (MgSO₄), filtered andconcentrated. The residue is purified by flash chromatography using 20%EtOAc in hexane as the eluent to afford 830.2 mg of the nitrobenzene. Mp115-116° C.; Anal. Calcd for C₁₁H₁₃FN₂O₂S: C, 51.55; H, 5.11; N, 10.93;S, 12.51. Found: C, 51.47; H, 5.12; N, 10.79; S, 12.42.

Step 4. To a stirred suspension of the nitrobenzene prepared in Step 3(5.5 g) in EtOH (260 mL) is added a solution of 2 M aqueous CuSO₄ (11.9mL). The mixture is cooled to 0° C. and NABH₄ (4.1 g) is added inportions. The reaction mixture turns very dark and is stirred at 0° C.for 10 min, at room temperature for 30 min, and then heated at refluxfor 3 h. The cooled reaction mixture is diluted with EtOAc (500 ml) andwashed with water (200 mL). The aqueous mixture is extracted with EtOAc(3×200 mL). The combined organics are dried (MgSO₄), filtered andconcentrated to afford the aniline intermediate.

Step 5. The dark residue from Step 4 is dissolved in 2:1 acetone/water(255 mL) and cooled to 0° C. To this stirred mixture is added solidNaHCO₃ (5.4 g) followed by benzylchloroformate (7.7 mL). The reactionmixture is stirred at 0° C. for 10 min, then at room temperature for 24h. The reaction mixture is quenched with 10% aqueous NaHSO₄ (200 mL) andthen poured into EtOAc (300 mL). The phases are separated and theaqueous phase is extracted with EtOAc (2×250 mL). The combined organicsare dried (MgSO₄), filtered and concentrated. The residue is purified byMPLC using 20% EtOAc in hexane to afford 6.03 g of the benzylcarbamateas a yellow solid. mp 72-74° C.; Anal. Calcd for C₁₉H₂₁FN₂O₂S: C, 63.31; H, 5.87; N, 7.77; S, 8.89. Found: C, 63.31; H, 5.97; N, 7.69; S,8.79.

Step 6. To a stirred solution of the carbamate from Step 5 (3.0 g) indry THF (33 mL) under N₂ cooled to −78° C., is added dropwise viasyringe a 1.6 M solution of nBuLi in hexane (5.4 mL). The reactionmixture was stirred at −78° C. for 35 min, then R-glycidyl butyrate (1.2mL) is added. The reaction mixture is stirred at −78° C. for 30 min,then at room temperature overnight during which time a precipitateforms. The reaction mixture is quenched with saturated aqueous NH₄Cl (33mL) and poured into EtOAc (100 mL). The phases are separated. Theorganic phase is washed with saturated aqueous NaHCO₃ (50 mL), brine (50mL), dried (MgSO₄), filtered and concentrated. The residue is purifiedby flash chromatography using EtOAc as the eluent to afford 2.5 g of ahydroxymethyl oxazolidinone. Mp 100-102° C. Anal. Calcd forC₁₅H₁₉FN₂O₃S: C, 55.20; H, 5.87; N, 8.58; S, 9.82. Found: C, 55.09; H,5.91; N, 8.36; S, 9.57.

Step 7. To a stirred solution of the alcohol prepared in Step 6 (1.7 g)in CH₂Cl₂ (35 mL) cooled to 0° C., is added triethylamine (1.1 mL)followed by methanesulfonyl chloride (0.5 mL). The reaction mixture isstirred at 0° C. for 10 min, then at room temperature for 1 h. Thereaction mixture is treated with water (35 mL). The phases are separatedand the aqueous phase is extracted with CH₂Cl₂ (35 mL). The combinedorganic phases are dried (MgSO₄), filtered and concentrated. The residueis purified by flash chromatography using 80% EtOAc in hexane as theeluent to afford 2.1 g of the mesylate. Mp 132-142° C. Anal. Calcd forC₁₆H₂₁FN₂O₅S₂: C, 47.51; H, 5.23; N, 6.93; S. 15.85. Found: C, 47.18; H,5.28; N, 6.84; S, 15.60.

Step 8. Ammonia gas is bubbled into a stirred suspension of the mesylateprepared in Step 7 (941.7 mg) in 1:1 THF/CH₃OH (40 mL) until saturated(approx. 5 min). The reaction mixture is heated in a sealed tube at 100°C. for 72 h. The cooled reaction mixture is concentrated to give thecrude amine, which is immediately suspended in CH₂Cl₂ (35 mL) and cooledto 0° C. To this stirred suspension is added triethylamine (0.97 mL, 6.9mmol) followed by di-tert-butyl dicarbonate (759.5 mg, 3.5 mmol). Thereaction mixture becomes homogeneous and is stirred at RT for 18 h. Thereaction mixture is poured into CH₂Cl₂ (75 mL) and washed with H₂O (1×50mL). The organic phase is dried (MgSO₄), filtered and concentrated. Theresulting residue is purified on a Biotage 40 S column using 30-35%ethyl acetate in CH₃OH as the eluent to afford 867.4 mg of the protectedamine. mp 74-75° C. Anal Cald: C, 56.45; H, 6.63; N, 9.88. Found: C,56.95; H, 6.85; N, 9.55.

Step 9. To a stirred suspension of the protected amine prepared in Step8 (205.2 mg) in 1:1 CH₃OH/H₂O (6 mL) cooled to 0° C. is added sodiummeta periodate (113.5 mg). The resulting suspension is stirred at RT for18 h. The reaction mixture is filtered and the solid is washed withCH₂Cl₂ (2×20 mL). The filtrate is extracted with H₂O (1×10 mL). Thephases are separated. The aqueous phase is extracted with CH₂Cl₂ (1×25mL). The combined organic phases are dried (MgSO₄), filtered andconcentrated. The white solid residue is purified on a Biotage 12 Mcolumn using 5% CH₃OH in CH₂Cl₂ as the eluent to afford 187.3 mg of thesulfoxide. mp 78-81° C.

Step 10. Dry HCl gas is passed over the surface of a stirred solution ofthe sulfoxide prepared in Step 9 (179.3 mg) in CH₃OH (2 mL) cooled to 0°C. for 1 minute. The reaction mixture is stirred at 0° C. for 10 min,then at room temperature for 15 min, then concentrated. The resultingyellow residue is suspended in THF (5 mL) and CH₂Cl₂ (5 mL) and cooledto 0° C. To this stirred suspension is added triethylamine (0.46 mL)followed by ethyldithioacetate (0.18 mL). The dark reaction mixture isstirred at RT overnight then concentrated. The dark residue is dilutedwith CH₂Cl₂ (30 mL) and washed with H₂O (2×15 mL). The organic phasesare dried (MgSO₄), filtered and concentrated. The dark residue ispurified on a Biotage 12 M column using 5% CH₃OH in CH₂Cl₂ as the eluentto afford 71.5 mg of the title compound as a tan solid. mp 85-89° C.

Following the general procedure outlined in Step 10 of Example 482, butsubstituting the dithioesters listed below, the compounds of Examples483 to 495 of Table K can be obtained.

TABLE K Example Dithioester No. Compound Amine (from Preparation Z) 483(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiazepineS-oxide

Z (a) 484 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (b) (tetrahydro-1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-methylpropanethio- amide, thiazepine S- oxide. 485(5S)-N-[[3-[3-Fluoro-4- Same as above Z (c) (tetrahydro-1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-cyclopropanecarbothio- amide, thiazepine S- oxide. 486(5S)-N-[[3-[3-Fluoro-4- Same as above Z (d) (tetrahydro-1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-butanethioamide, thiazepine S-oxide 487 (5S)-N-[[3-[3-Fluoro-4- Same asabove Z (e) (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5-oxazolidinyl]methyl]-3- methylbutanethioamide, thiazepine S-oxide 488(5S)-N-[[3-[3-Fluoro-4- Same as above Z (f) (tetrahydro-1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-methylbutanethioamide, thiazepine S-oxide 489 (5S)-N-[[3-[3-Fluoro-4-Same as above Z (g) (tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]- 3,3-dimethylbutanethio- amide,thiazepine S- oxide 490 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (h)(tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclobutanecarbothio- amide, thiazepine S- oxide491 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (i) (tetrahydro-1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-1-cyclopentanecarbothio- amide, thiazepine S- oxide 492(5S)-N-[[3-[3-Fluoro-4- Same as above Z (j) (tetrahydro-1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-cyclohexanecarbothio- amide, thiazepine S- oxide 493(5S)-N-[[3-[3-Fluoro-4- Same as above Z (k) (tetrahydro-1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-cyclopropylethanethio- amide, thiazepine S- oxide 494(5S)-N-[[3-[3-Fluoro-4- Same as above Z (l) (tetrahydro-1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-cyclobutylethanethio- amide, thiazepine S- oxide 495(5S)-N-[[3-[3-Fluoro-4- Same as above Z (m) (tetrahydro-1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-cyclopentylethanethio- amide, thiazepine S- oxide

EXAMPLE 496(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide,thiazepine S-oxide

The title compound can be prepared by the procedure of Example 482, bysubstituting an appropriate quantity of 2,6-difluoro-4-nitrobenzene(trifluoromethane) sulfonate for 3,4-difluoronitrobenzene in Step 1.

Utilizing the amine prepared in Example 496, but substituting thedithioester listed below for ethyl dithioacetate in the final step, thecompounds of Examples 497 to 499 of Table L are obtained.

TABLE L Example Dithioester No. Compound Amine (from Preparation Z) 497(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiazepineS-oxide

Z (a) 498 (5S)-N-[[3-[3,5- Same as above Z (b) Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-methylpropanethio- amide, thiazepine S- oxide 499 (5S)-N-[[3-[3,5- Sameas above Z (c) Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide,thiazepine S- oxide

EXAMPLE 500(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide,thiazepine S-oxide

The title compound can be prepared by the procedure of Example 482, bysubstituting an appropriate quantity of 4-fluoronitrobenzene for3,4-difluoronitro-benzene in Step 1.

Utilizing the amine prepared in Example 500, but substituting thedithioester listed below for ethyl dithioacetate in the final step, thecompounds of Examples 501 to 503 of Table M are obtained

TABLE M Example Dithioester No. Compound Amine (from Preparation Z) 501(5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide, thiazepine S-oxide

Z (a) 502 (5S)-N-[[3-[4- Same as above Z (b) (Tetrahydro-1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-methylpropanethio- amide, thiazepine S- oxide 503 (5S)-N-[[3-[4- Same asabove Z (c) (Tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothio- amide, thiazepine S- oxide

EXAMPLE 504(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamnide,thiazepine S,S-dioxide

Step 1. To a stirred solution of the thiazepine prepared in Step 8 ofExample 482 (243.7 mg) in 25% H₂O/acetone (8 mL) is added4-methylmorpholine N-oxide (201.5 mg) followed by a solution of osmiumtetroxide in 2-methyl-2-propanol (2.5 wt %, 30 μL). The reaction mixtureis stirred at room temperature for 18 h. The reaction mixture is treatedwith saturated sodium bisulfate (8 mL), then poured into CH₂Cl₂ (50 mL).The phases are separated. The aqueous phase is extracted with CH₂Cl₂(2×25 mL). The combined organic phases are washed with brine (1×25 mL),dried (MgSO₄), filtered and concentrated. The residue is purified on aBiotage 40 S column using 1% CH₃OH in CH₂Cl₂ as the eluent to afford216.1 mg (0.47 mmol, 83%) of the thiazepine S,S-dioxide as a whitesolid. mp 144-146° C.

Step 2. Dry HCl gas is passed over the surface of a stirred solution ofthe thiazepine S,S-dioxide prepared in Step 1 (108.2 mg) in CH₃OH(3 mL)at 0° C. for 1 minute. The reaction mixture is stirred at 0° C. for 10min and then at room temperature for 15 min. The reaction isconcentrated and the yellow residue is suspended in CH₂Cl₂ (2 mL) andTHF (2 mL). This stirred suspension is cooled to 0° C. and triethylamine(0.27 mL) is added followed by a solution of ethyldithioacetate (0.11mL) in THF (0.5 mL) with 0.25 mL rinse. The yellowish-green solution isstirred at 0° C. for 10 min then at room temperature for 18 h. Thereaction mixture is poured into CH₂Cl₂ (20 mL) and washed with H₂O (2×10mL). The organic phase was dried (MgSO₄), filtered and concentrated. Theresidue is purified on a Biotage 12 M column using 2% CH₃OH in CH₂Cl₂ asthe eluent to afford 77.3 mg of the title compound as a white solid. mp88-90° C.

Following the general procedure outlined in Step 2 of Example 504, butsubstituting the dithioester listed below for ethyl dithioacetate, thecompounds of Examples 505 to 507 of Table N are obtained.

TABLE N Example Dithioester No. Compound Amine (from Preparation Z) 505(5S)-N-[[3-[3-Fluoro-4- (4-thiomorpholinyl]- phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide, thiazepine S,S-dioxide

Z (a) 506 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (b)(4-thiomorpholinyl]- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-methylpropanethio- amide, thiazepine S,S- dioxide 507(5S)-N-[[3-[3-Fluoro-4- Same as above Z (c) (4-thiomorpholinyl]-phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide,thiazepine S,S- dioxide

EXAMPLE 508(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide,thiazepine S,S-dioxide

The title compound can be prepared by the procedures of Examples 504 and482, by substituting an appropriate quantity of2,6-difluoro-4-nitrobenzene (trifluoromethane) sulfonate for3,4-difluoronitrobenzene in Step 1 of Example 482.

Utilizing the amine prepared in Example 508, but substituting thedithioester listed below for ethyl dithioacetate in the final step, thecompounds of Examples 509 to 511 of Table O are obtained.

TABLE O Example Dithioester No. Compound Amine (from Preparation Z) 509(5S)-N-[[3-[3,5- Difluoro-4-(4- thiomorpholinyl]- phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide, thiazepine S,S-dioxide

Z (a) 510 (5S)-N-[[3-[3,5- Same as above Z (b) Difluoro-4-(4-thiomorpholinyl]- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-methylpropanethio- amide, thiazepine S,S- dioxide 511 (5S)-N-[[3-[3,5-Same as above Z (c) Difluoro-4-(4- thiomorpholinyl]- phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothio- amide, thiazepine S,S-dioxide

EXAMPLE 512(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide,thiazepine S,S-dioxide

The title compound can be prepared by the procedure of Examples 504 and482, by substituting an appropriate quantity of 4-fluoronitrobenzene for3,4-difluoronitro-benzene in Step 1 of Example 482.

Utilizing the amine prepared in Example 512, but substituting thedithioester listed below for ethyl dithioacetate in the final step, thecompounds of Examples 513 to 515 of Table P are obtained.

TABLE P Example Dithioester No. Compound Amine (From Preparation Z) 513(5S)-N-[[3-[4- (tetrahydro-1,4- thiazepin-4(5H)- yl))phenyl]-2-oxo-5-oxazolidinyl]- methyl]propanethio- amide, thiazepine S,S- dioxide

Z (a) 514 (5S)-N-[[3-[4- Same as above Z (b) (tetrahydro-1,4-thiazepin-4(5H)- yl))phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-methylpropanethio- amide, thiazepine S,S- dioxide 515 (5S)-N-[[3-[4-Same as above Z (c) (tetrahydro-1,4- thiazepin-4(5H)-yl))phenyl]-2-oxo-5- oxazolidinyl]- methyl]cyclopropane- carbothioamide,thiazepine S,S-dioxide

EXAMPLE 516(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide

This compound is prepared according to the procedure of Step 8 inExample 482, but stubstituting an appropriate quantity of ethyldithioacetate for di-tert-butyl dicarbonate; mp 129-131° C.

Utilizing the amine prepared in Step 8 of Example 482, but substitutingan appropriate quantity of the dithioester listed below fordi-tert-butyl dicarbonate, the compounds of Examples 517 to 529 of TableQ are obtained.

TABLE Q Example Dithioester No. Compound Amine (From Preparation Z) 517(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide

Z (a) 518 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (b) (tetrahydro-1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-methylpropanethioamide 519 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (c)(tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothio- amide 520(5S)-N-[[3-[3-Fluoro-4- Same as above Z (d) (tetrahydro-1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-butanethioamide 521 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (e)(tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5-oxazolidinyl]methyl]-3- methylbutanethioamide 522(5S)-N-[[3-[3-Fluoro-4- Same as above Z (f) (tetrahydro-1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-methylbutanethioamide 523 (5S)-N-[[3-[3-Fluoro-4- Same as above Z (g)(tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5-oxazolidinyl]methyl]- 3,3-dimethylbutanethio- amide 524(5S)-N-[[3-[3-Fluoro-4- Same as above Z (h) (tetrahydro-1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-cyclobutanecarbothio- amide 525 (5S)-N-[[3-[3-Fluoro-4- Same as above Z(i) (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopentanecarbothio- amide 526(5S)-N-[[3-[3-Fluoro-4- Same as above Z (j) (tetrahydro-1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-cyclohexanecarbothio- amide 527 (5S)-N-[[3-[3-5 Fluoro- Same as above Z(k) 4-(tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- cyclopropylethanethio- amide 528(5S)-N-[[3-[3-Fluoro-4- Same as above Z (l) (tetrahydro-1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-cyclobutylethanethio- amide 529 (5S)-N-[[3-[3-Fluoro-4- Same as above Z(m) (tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- cyclopentylethanethio- amide

EXAMPLE 530(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide

This compound can be prepared according to the procedures of Example 482and Example 516, but substituting an appropriate quantity of2,6-difluoro-4-nitrophenyl trifluoromethane sulfonate for3,4-difluoronitrobenzene in Step 1 of Example 482.

Utilizing the amine prepared in Example 530, but substituting anappropriate quantity of the dithioester listed below for di-tert-butyldicarbonate, the compounds of Examples 531 to 533 of Table R can beprepared.

TABLE R Example Dithio Compound No. Compound Amine (from Preparation Z)531 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide

Z (a) 532 (5S)-N-[[3-[3,5- Same as above Z (b) Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-methylpropanethioamide 533 (5S)-N-[[3-[3,5- Same as above Z (c)Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothio- amide

EXAMPLE 534(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide;mp 129-131° C.

This compound can be prepared according to the procedures of Example 482and Example 516, but substituting an appropriate quantity of4-fluoronitrobenzene for 3,4-difluoronitrobenzene in Step 1 of Example482.

Utilizing the amine prepared in Example 534, but substituting anappropriate quantity of the dithioester listed below for di-tert-butyldicarbonate, the compounds of Examples 535 to 537 of Table S can beprepared.

TABLE S Example Dithio Compound No. Compound Amine (from Preparation Z)535 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]- methyl]propanethio- amide

Z (a) 536 (5S)-N-[[3-[4- Same as above Z (b) (Tetrahydro-1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-methylpropanethioamide 537 (5S)-N-[[3-[4- Same as above Z (c)(Tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]-methyl]cyclopropane- carbothioamide

EXAMPLE 538(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea,thiazepine S-oxide

This compound can be prepared by the procedure described in Example 33,but substituting the amine prepared in Example 482 for the amine 33.

By reaction of the isothiocyanate prepared in Example 538 with theamines and alcohols listed in Table T, the compounds of Examples 539 to544 can be prepared.

TABLE T Example Amine or No. Compound Isothiocyanate Alcohol 539(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′- methylthiourea, thiazepineS-oxide

CH₃NH₂ 540 (5S)-N-[[3-[3-Fluoro-4- Same as above (CH₃)₂NH(tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]- N′,N′-dimethylthiourea, thiazepine S-oxide 541(5S)-N-[[3-[3-Fluoro-4- Same as above Azetidine (tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1-azetidinecarbothioamide, thiazepine S-oxide 542 (5S)-N-[[3-[3-Fluoro-4-Same as above CH₃OH (tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate,thiazepine S-oxide 543 (5S)-N-[[3-[3-Fluoro-4- Same as above CH₃CH₂OH(tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O- ethylthiocarbamate, thiazepine S-oxide 544(5S)-N-[[3-[3-Fluoro-4- Same as above (CH₃)₂CHOH (tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-isopropylthiocarbamate, thiazepine S-oxide

EXAMPLE 545(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea,thiazepine S-oxide

This compound can be prepared by the procedure described in Example 33,but substituting the amine prepared in Example 496 for the amine 33.

By reaction of the isothiocyan ate prepared in Example 545 with theamines and alcohols listed in Table U, the compounds of Examples 546 to551 can be prepared.

TABLE U Example Amine or No. Compound Isothiocyanate Alcohol 546(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′- methylthiourea, thiazepineS-oxide

CH₃NH₂ 547 (5S)-N-[[3-[3,5- Same as above (CH₃)₂NHDifluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]- N′,N′-dimethylthiourea, thiazepine S-oxide 548(5S)-N-[[3-[3,5- Same as above Azetidine Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1-azetidinecarbothioamide, thiazepine S-oxide 549 (5S)-N-[[3-[3,5- Same asabove CH₃OH Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate,thiazepine S-oxide 550 (5S)-N-[[3-[3,5- Same as above CH₃CH₂OHDifluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O- ethylthiocarbamate, thiazepine S-oxide 551(5S)-N-[[3-[3,5- Same as above (CH₃)₂CHOH Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-isopropylthiocarbamate, thiazepine S-oxide

EXAMPLE 552(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea,thiazepine S-oxide

This compound can be prepared by the procedure described in Example 33,but substituting the amine prepared in Example 500 for the amine 33.

By reaction of the isothiocyanate prepared in Example 552 with theamines and alcohols listed in Table V, the compounds of Examples 553 to558 can be prepared.

TABLE V Example Amine or No. Compound Isothiocyanate Alcohol 553(5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′- methylthiourea, thiazepine S-oxide

CH₃NH₂ 554 (5S)-N-[[3-[4- Same as above (CH₃)₂NH (Tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′,N′-dimethylthiourea, thiazepine S-oxide 555 (5S)-N-[[3-[4- Same asabove Azetidine (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-1- azetidinecarbothioamide, thiazepine S-oxide 556(5S)-N-[[3-[4- Same as above CH₃OH (Tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate,thiazepine S-oxide 557 (5S)-N-[[3-[4- Same as above CH₃CH₂OH(Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O- ethylthiocarbamate, thiazepine S-oxide 558(5S)-N-[[3-[4- Same as above (CH₃)₂CHOH (Tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-isopropylthiocarbamate, thiazepine S-oxide

EXAMPLE 559(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]rmethyl]thiourea,thiazepine S,S-dioxide

This compound can be prepared by the procedure described in Example 33,but substituting the amine prepared in Example 504 for the amine 33.

By reaction of the isothiocyanate prepared in Example 559 with theamines and alcohols listed in Table W, the compounds of Examples 560 to565 can be prepared.

TABLE W Example Amine or No. Compound Isothiocyanate Alcohol 560(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′- methylthiourea, thiazepineS,S-dioxide

CH₃NH₂ 561 (5S)-N-[[3-[3-Fluoro-4- Same as above (CH₃)₂NH(tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]- N′,N′-dimethylthiourea, thiazepine S,S-dioxide 562(5S)-N-[[3-[3-Fluoro-4- Same as above Azetidine (tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1-azetidinecarbothioamide, thiazepine S,S-dioxide 563(5S)-N-[[3-[3-Fluoro-4- Same as above CH₃OH (tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthiocarbamate, thiazepine S,S-dioxide 564 (5S)-N-[[3-[3-Fluoro-4-Same as above CH₃CH₂OH (tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- ethylthiocarbamate,thiazepine S,S-dioxide 565 (5S)-N-[[3-[3-Fluoro-4- Same as above(CH₃)₂CHOH (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O- isopropylthiocarbamate, thiazepine S,S-dioxide

EXAMPLE 566(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea,thiazepine S,S-dioxide

This compound can be prepared by the procedure described in Example 33,but substituting the amine prepared in Example 508 for the amine 33.

By reaction of the isothiocyanate prepared in Example 566 with theamines and alcohols listed in Table X, the compounds of Examples 561 to572 can be prepared.

TABLE X Example Amine or No. Compound Isothiocyanate Alcohol 567(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′- methylthiourea, thiazepineS,S-dioxide

CH₃NH₂ 568 (5S)-N-[[3-[3,5- Same as above (CH₃)₂NHDifluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]- N′,N′-dimethylthiourea, thiazepine S,S-dioxide 569(5S)-N-[[3-[3,5- Same as above Azetidine Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1-azetidinecarbothioamide, thiazepine S,S-dioxide 570 (5S)-N-[[3-[3,5-Same as above CH₃OH Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate,thiazepine S,S-dioxide 571 (5S)-N-[[3-[3,5- Same as above CH₃CH₂OHDifluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O- ethylthiocarbamate, thiazepine S,S-dioxide 572(5S)-N-[[3-[3,5- Same as above (CH₃)₂CHOH Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-isopropylthiocarbamate, thiazepine S,S-dioxide

EXAMPLE 573(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea,thiazepine S,S-dioxide

This compound can be prepared by the procedure described in Example 33,but substituting the amine prepared in Example 512 for the amine 33.

By reaction of the isothiocyanate prepared in Example 573 with theamines and alcohols listed in Table Y, the compounds of Examples 574 to579 can be prepared.

TABLE Y Example Amine or No. Compound Isothiocyanate Alcohol 574(5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′- methylthiourea, thiazepine S,S-dioxide

CH₃NH₂ 575 (5S)-N-[[3-[4- Same as above (CH₃)₂NH (Tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′,N′-dimethylthiourea, thiazepine S,S-dioxide 576 (5S)-N-[[3-[4- Sameas above Azetidine (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-1- azetidinecarbothioamide, thiazepine S,S-dioxide577 (5S)-N-[[3-[4- Same as above CH₃OH (Tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate,thiazepine S,S-dioxide 578 (5S)-N-[[3-[4- Same as above CH₃CH₂OH(Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O- ethylthiocarbamate, thiazepine S,S-dioxide 579(5S)-N-[[3-[4- Same as above (CH₃)₂CHOH (Tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-isopropylthiocarbamate, thiazepine S,S-dioxide

EXAMPLE 580(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea

This compound can be prepared by the procedure described in Example 33,but substituting the amine prepared in Step 8 of Example 482 for theamine 33.

By reaction of the isothiocyanate prepared in Example 580 with theamines and alcohols listed in Table Z, the compounds of Examples 581 to586 can be prepared.

TABLE Z Example Amine or No. Compound Isothiocyanate Alcohol 581(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′- methylthiourea

CH₃NH₂ 582 (5S)-N-[[3-[3-Fluoro-4- Same as above (CH₃)₂NH(tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]- N′,N′-dimethylthiourea 583 (5S)-N-[[3-[3-Fluoro-4-Same as above Azetidine (tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- azetidinecarbothioamide 584(5S)-N-[[3-[3-Fluoro-4- Same as above CH₃OH (tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthiocarbamate 585 (5S)-N-[[3-[3-Fluoro-4- Same as above CH₃CH₂OH(tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O- ethylthiocarbamate 586 (5S)-N-[[3-[3-Fluoro-4-Same as above (CH₃)₂CHOH (tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- isopropylthiocarbamate

EXAMPLE 587(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea

This compound can be prepared by the procedure described in Example 33,but substituting the amine prepared in Example 530 for thc amine 33.

By reaction of the isothiocyanate prepared in Example 587 with theamines and alcohols listed in Table AA, the compounds of Examples 588 to593 can be prepared.

TABLE AA Example Amine or No. Compound Isothiocyanate Alcohol 588(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′- methylthiourea

CH₃NH₂ 589 (5S)-N-[[3-[3,5- Same as above (CH₃)₂NHDifluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]- N′,N′-dimethylthiourea 590 (5S)-N-[[3-[3,5- Sameas above Azetidine Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- azetidinecarbothioamide 591(5S)-N-[[3-[3,5- Same as above CH₃OH Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthiocarbamate 592 (5S)-N-[[3-[3,5- Same as above CH₃CH₂OHDifluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O- ethylthiocarbamate 593 (5S)-N-[[3-[3,5- Same asabove (CH₃)₂CHOH Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- isopropylthiocarbamate

EXAMPLE 594(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea

This compound can be prepared by the procedure described in Example 33,but substituting the amine prepared in Example 534 for the amine 33.

By reaction of the isothiocyanate prepared in Example 594 with theamines and alcohols listed in Table BB, the compounds of Examples 595 to600 can be prepared.

TABLE BB Example Amine or No. Compound Isothiocyanate Alcohol 595(5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′- methylthiourea

CH₃NH₂ 596 (5S)-N-[[3-[4- Same as above (CH₃)₂NH (Tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′,N′-dimethylthiourea 597 (5S)-N-[[3-[4- Same as above Azetidine(Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-1- azetidinecarbothioamide 598 (5S)-N-[[3-[4- Sameas above CH₃OH (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O- methylthiocarbamate 599 (5S)-N-[[3-[4- Same asabove CH₃CH₂OH (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O- ethylthiocarbamate 600 (5S)-N-[[3-[4- Same asabove (CH₃)₂CHOH (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O- isopropylthiocarbamate

What is claimed:
 1. A compound of the formula I

or a pharmaceutical acceptable salt thereof wherein:

R₁ is a) H, b) NH₂, c) NHC₁₋₄alkyl, d) C₁₋₄ alkyl, e) —OC₁₋₄ alkyl, f)—SC₁₋₄ alkyl, g) C₁₋₄ alkyl substituted with one to three fluoro, one totwo chloro, CN or —COOC₁₋₄ alkyl, h) C₃₋₆cycloalkyl, i) N(C₁₋₄alkyl)₂,or j) N(CH₂)₂₋₅;

R₂₃ and R₂₄ are independently a) H, b) F, c) Cl, d) C₁₋₂alkyl, e) CN, f)OH, g) C₁₋₂alkoxy, h) nitro, or i) amino;

Z² is a) —O₂S—, b) —O—, c) —OS—, or d) —S—; and w is
 2. 2. A compound offormula I as shown in claim 1 which is


3. A compound of claim 2 wherein R₂₃ is H and R₂₄ is F.
 4. A compound ofclaim 2 wherein Z² is —SO₂—, —SO—, or —S—.
 5. A compound of claim 2wherein Z² is —O—.
 6. A compound of claim 4 or 5 wherein R₁ isC₁-C₄alkyl, NH₂, C₃-C₄cycloalkyl, OC₁-C₄alkyl, NHC₁-C₄alkyl, orN(C₁-C₄)alkyl.
 7. A compound of claim 1 which is 1)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide,thiazepine S-oxide; 2)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]propanethioamide,thiazepine S-oxide; 3)(S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]-methyl]-2-methylpropanethioamide,thiazepine S-oxide; 4)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothio-amide,thiazepine S-oxide; 5)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]butanethioamide,thiazepine S-oxide; 6)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]butanethioamide,thiazepine S-oxide; 7)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylbutanethioamide,thiazepine S-oxide; 8)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]-3,3-dimethylbutanethioamide,thiazepine S-oxide; 9)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclobutanecarbothioamide,thiazepine S-oxide; 10) 10)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-cyclopentanecarbothioamide,thiazepine S-oxide; 11)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclohexanecarbothioamide,thiazepine S-oxide; 12)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-cyclopropylethanethioamide,thiazepine S-oxide; 13)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyll-2-cyclobutylethanethioamide,thiazepine S-oxide; 14)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-cyclopentylethanethioamide,thiazepine S-oxide; 15)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide,thiazepine S-oxide; 16)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]propanethioamide,thiazepine S-oxide; 17)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide,thiazepine S-oxide; 18)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropanecaibothioamide,thiazepine S-oxide; 19)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide,thiazepine S-oxide; 20)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]propanethioamide,thiazepine S-oxide; 21)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazcpin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide,thiazepine S-oxide; 22)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothioamide, thiazepine S-oxide; 23)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide,thiazepine S,S-dioxide; 24)(5S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-propanethioamide,thiazepine S,S-dioxide; 25)(5S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide,thiazepine S,S-dioxide; 26)(5S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide,thiazepine S,S-dioxide; 27)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide,thiazepine S,S-dioxide; 28)(5S)-N-[[3-[3,5-Difluoro-4-(4-thiomorpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-propanethioamide,thiazepine S,S-dioxide; 29)(5S)-N-[[3-[3,5-Difluoro-4-(4-thiomorpholinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]-2-methylpropanethioamide,thiazcpine S,S-dioxide; 30)(5S)-N-[[3-[3,5-Difluoro-4-(4-thiomorpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide,thiazepine S,S-dioxide; 31)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide,thiazepine S,S-dioxide; 32)(5S)-N-[[3-[4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]propanethioamide,thiazepine S,S-dioxide; 33)(5S)-N-[[3-[4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide,thiazepine S,S-dioxide; 34)(5S)-N-[[3-[4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]-methyl]cyclopropanecarbothioamide,thiazepine S,S-dioxide; 35)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide;36)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]propanethioamide;37)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide:38)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothioamide;39)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]butanethioamide;40) (5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl ))phenyl]-2-oxo-5-oxazolidinyl]methyl]-3-methylbutanethioamide; 41)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylbutanethioamide;42)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]-3,3-dimethylbutanethioamide;43)(5S)-N-[[3-[3-Fluoro-4-(tctrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclobutanecarbothioamide;44)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopentanecarbothioamide;45)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclohexanccarbothioamide;46) (5S)-N-[[3-[3-5 Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-cyclopropylethanethioamide,47)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-cyclobutylethanethioamide,48)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-cyclopentylethanethioamide;49)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide;50)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]propanethioamide;51)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide;52)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothioamide;53)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide;54)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]-methyl]propanethioamide;55)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]-methyl]-2-methylpropanethioamide;56)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl))phenyl]-2-oxo-5-oxazolidinyl]-methyl]cyclopropanecarbothioamide;57)(SS)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea,thiazepine S-oxide; 58)SS)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′-methylthiourea,thiazepine S-oxide; 59)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′-dimethylthiourea,thiazepine S-oxide; 60)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamide,thiazepine S-oxide; 61)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate,thiazepine S-oxide; 62)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthiocarbamate,thiazepine S-oxide; 63)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-isopropylthiocarbamate,thiazepine S-oxide; 64)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea,thiazepine S-oxide; 65)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′-methylthiourea,thiazepine S-oxide; 66)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′-dimethylthiourea,thiazepine S-oxide; 67)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamide,thiazepine S-oxide; 68) (5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate,thiazepine S-oxide; 69)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthiocarbamate,thiazepine S-oxide; 70)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-isopropylthiocarbamate,thiazepine S-oxide; 71)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea,thiazepine S-oxide; 72)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′-methylthiourea,thiazepine S-oxide; 73)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′-dimethylthiourea,thiazcpinc S-oxide; 74)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamide,thiazepine S-oxide; 75)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate,thiazepine S-oxide; 76)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate,thiazcpine S-oxide; 77)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazcpin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-isopropylthiocarbamate,thiazepine S-oxide; 78)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea,thiazepine S,S-dioxide; 79) (5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′-methylthiourea,thiazepine S,S-dioxide; 80)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′-dimethylthiourea,thiazcpine S,S-dioxide; 81)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazcpin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamide,thiazepine S,S-dioxide; 82)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate,thiazepine S,S-dioxide; 83)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthiocarbamate,thiazepine S,S-dioxide; 84)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-isopropylthiocarbamate,thiazcpine S,S-dioxide; 85)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea,thiazepine S,S-dioxide; 86)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′-methylthiourea,thiazepine S,S-dioxide; 87)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′-dimethylthiourea,thiazepine S,S-dioxide; 88)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamide,thiazepine S,S-dioxide; 89)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazcpin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate,thiazepine S,S-dioxide; 90)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthiocarbamate,thiazepine S,S-dioxide; 91)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-isopropylthiocarbamate,thiazepine S,S-dioxide; 92)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea,thiazepine S,S-dioxide; 93)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepln-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′-methylthiourea,thiazepine S,S-dioxide; 94)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′-dimethylthiourea,thiazepine S,S-dioxide; 95)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamide,thiazepine S,S-dioxide; 96)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate,thiazepine S,S-dioxide; 97)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthiocarbamate,thiazepine S,S-dioxide; 98)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-isopropylthiocarbamate,thiazepine S,S-dioxide; 99)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea;100)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′-methylthiourea;101)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′-dimethylthiourea;102)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamide;103)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate;104)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthiocarbamate;105)(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-isopropylthiocarbamate;106)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea;107)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′-methylthiourea;108)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′-dimethylthiourea;109)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamide;110)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate;111)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthiocarbamate;112)(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-isopropylthiocarbamate;113)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea;114)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′-methylthiourea;115)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′-dimethylthiourea;116)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-azetidinccarbothioamide;117)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate;118)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthiocarbamate;119)(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-isopropylthiocarbamate.8. A method for treating microbial infections in patients comprisingadministering to a patient in need thereof an effective amount of acompound of formula I as shown in claim
 1. 9. The method of claim 8wherein said compound of formula I is administered, orally,parenterally, or topically.
 10. The method of claim 8 wherein saidcompound is administered in an amount of from about 0.1 to about 100mg/kg of body weight/day.
 11. A pharmaceutical composition comprising acompound of claim 1 and pharmaceutically acceptable carrier.